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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-000185-22 | EudraCT Number | ||
| KEYNOTE-034 | Other Identifier | Merck Sharp & Dohme Corp. |
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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The primary objectives of the Phase 1b part of the study are to evaluate the safety, as assessed by incidence of dose limiting toxicity (DLT), of talimogene laherparepvec in combination with pembrolizumab in adults with previously untreated, unresectable, stage IIIB to IVM1c melanoma.
The primary objective of Phase 3 are to evaluate the efficacy of talimogene laherparepvec with pembrolizumab versus placebo with pembrolizumab, as assessed by progression-free survival (PFS) (response evaluation by blinded independent central review using modified Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) and overall survival (OS).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1b: Talimogene Laherparepvec + Pembrolizumab | Experimental | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ plaque-forming units (PFU)/mL by intralesional injection. Subsequent doses of talimogene laherparepvec at up to 4 mL of 10⁸ PFU/mL began 3 weeks after the first dose and were administered every 2 weeks until disappearance of injectable lesions, complete response (CR), confirmed disease progression (PD) per modified Immune-related Response Criteria (irRC), intolerance of study treatment, 24 months from the date of the first dose of pembrolizumab, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 2 weeks starting at the time of the third dose of talimogene laherparepvec (week 6) until confirmed PD per modified irRC, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
|
| Phase 3 : Placebo + Pembrolizumab | Placebo Comparator | Participants received up to 4 mL placebo to talimogene laherparepvec by intralesional injection on day 1 of week 0. Subsequent doses of placebo (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, complete response per modified Immune-related Response Criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST) (iCR), confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of placebo, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
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| Phase 3: Talimogene Laherparepvec + Pembrolizumab |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Talimogene Laherparepvec | Drug | Talimogene laherparepvec administered by intratumoral injection |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs) | A DLT was defined as any toxicity related to study drug which met any of the following criteria based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0:
| The DLT evaluation period was 6 weeks from the initial administration of pembrolizumab (week 6 to 12). |
| Phase 3: Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) Assessed Using Modified RECIST 1.1 | PFS per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 is defined as the interval from randomization to the earlier event of progressive disease (PD) per modified RECIST 1.1 or death from any cause. PD: Increase in size of target lesions from nadir by ≥ 20% and ≥ 5 mm absolute increase above nadir, or the appearance of a new lesion. Median PFS was calculated using the Kaplan-Meier method. Participants without an event were censored at their last evaluable tumor assessment if available; otherwise on their randomization date. The primary analysis of PFS was specified to be conducted when 407 PFS events had occurred (data cut-off date 02 March 2020). | From randomization until the data-cut-off date of 02 March 2020; median (range) time on follow-up was 25.5 (0.6, 44.7) months in the Placebo + Pembrolizumab arm and 25.6 (0.3, 45.8) months in the Talimogene Laherparepvec + Pembrolizumab arm. |
| Phase 3: Overall Survival | Overall survival (OS) is defined as the interval from randomization to death from any cause. Median overall survival was calculated using the Kaplan-Meier method. Participants without an event were censored at their last known alive date. |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1b: Objective Response Rate (ORR) | ORR is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) using the modified Immune-related Response Criteria (irRC), by Investigator assessment. CR was defined as the disappearance of all lesions; PR was defined as a decrease in tumor area ≥ 50% relative to baseline, response must have been confirmed by a second, consecutive assessment at least 4 weeks apart. Radiographic imaging for assessment of lesions was performed using computed tomography (CT), positron emission tomography (PET), magnetic resonance imaging (MRI), or ultrasound. Clinical measurement of cutaneous, subcutaneous, and palpable nodal tumor lesions was conducted with calipers. |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Birmingham | Alabama | 35243 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28886381 | Background | Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka RHI, Michielin O, Olszanski AJ, Malvehy J, Cebon J, Fernandez E, Kirkwood JM, Gajewski TF, Chen L, Gorski KS, Anderson AA, Diede SJ, Lassman ME, Gansert J, Hodi FS, Long GV. Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Cell. 2017 Sep 7;170(6):1109-1119.e10. doi: 10.1016/j.cell.2017.08.027. | |
| 28238174 |
| Label | URL |
|---|---|
| AmgenTrials clinical trials website | View source |
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De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication (or other new use) have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the link below.
In Phase 3 participants were randomized equally to 1 of 2 arms. Randomization was stratified by stage of disease: less advanced stages (IIIB, IIIC, and IVM1a) versus more advanced stages (IVM1b and IVM1c) and by prior serine/threonine protein kinase B-Raf (BRAF) inhibitor therapy (no prior BRAF inhibitor versus BRAF inhibitor with or without mitogen-activated extracellular signal-regulated kinase [MEK] inhibitor).
This study was conducted at 134 centers in Australia, Canada, Europe, South Africa, South Korea, and the United States.
Phase 1b was an open-label, single-arm study and Phase 3 was a randomized, double-blind, placebo-controlled study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1b: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ plaque-forming units (PFU)/mL by intralesional injection on day 1 of week 1. Subsequent doses of talimogene laherparepvec at up to 4 mL of 10⁸ PFU/mL began 3 weeks after the first dose and were administered every 2 weeks until disappearance of injectable lesions, complete response (CR), confirmed disease progression (PD) per modified Immune-related Response Criteria (irRC), intolerance of study treatment, 24 months from the date of the first dose of pembrolizumab, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 2 weeks starting at the time of the third dose of talimogene laherparepvec (week 6) until confirmed PD per modified irRC, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jan 15, 2020 | Mar 8, 2022 |
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Phase 1b was an open-label, single-arm study. Phase 3 was a randomized, double-blind, placebo-controlled study design.
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| Experimental |
Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
|
|
| Pembrolizumab | Drug | Administered at a dose of 200 mg as an intravenous infusion over approximately 30 minutes. |
|
|
| Placebo | Drug | Administered by intratumoral injection |
|
| From randomization until the end of study; median (range) time on follow-up was 34.8 (0.6, 58.3) months in the Placebo + Pembrolizumab arm and 36.8 (0.3, 58.4) months in the Talimogene Laherparepvec + Pembrolizumab arm. |
| Tumor assessments were performed at week 6 (prior to initiation of pembrolizumab), week 18, and every 12 weeks thereafter until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 58.6 (1.4, 61.6) months. |
| Phase 1b: Best Overall Response (BOR) | Best overall response is defined as the best overall visit response in the following order: CR, PR, stable disease (SD), progressive disease (PD), or unevaluable (UE), based on investigator assessment using the modified irRC up to the start of any subsequent anti-cancer therapy. CR was defined as the disappearance of all lesions; PR was defined as a decrease in tumor area ≥ 50% relative to baseline; PD was defined as an increase in tumor area ≥ 25% relative to nadir; and SD was defined as any outcome not meeting the criteria for response or PD with ≥ 77 days elapsed after enrollment. Responses and PD must have been confirmed by a second, consecutive assessment at least 4 weeks apart. | Tumor assessments were performed at week 6 (prior to initiation of pembrolizumab), week 18, and every 12 weeks thereafter until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 58.6 (1.4, 61.6) months. |
| Phase 1b: Durable Response Rate (DRR) | DRR is defined as the percentage of participants with a best overall response of CR or PR using the modified irRC per Investigator assessment with a duration of response of at least 6 months. CR was defined as the disappearance of all lesions; PR was defined as a decrease in tumor area ≥ 50% relative to baseline, response must have been confirmed by a second, consecutive assessment at least 4 weeks apart. | Tumor assessments were performed at week 6 (prior to initiation of pembrolizumab), week 18, and every 12 weeks thereafter until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 58.6 (1.4, 61.6) months. |
| Phase 1b: Duration of Response (DOR) | Duration of response (DOR) is defined as the time from the date of an initial response (CR or PR) that is subsequently confirmed to the earlier of confirmed PD or death. Participants who had not ended their response at the time of analysis were censored at their last evaluable tumor assessment before start of the first subsequent anticancer therapy. CR was defined as the disappearance of all lesions; PR was defined as a decrease in tumor area ≥ 50% relative to baseline; PD was defined as an increase in tumor area ≥ 25% relative to nadir. Response and PD must have been confirmed by a second, consecutive assessment at least 4 weeks apart. | Tumor assessments were performed at week 6 (prior to initiation of pembrolizumab), week 18, and every 12 weeks thereafter until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 58.6 (1.4, 61.6) months. |
| Phase 1b: Disease Control Rate (DCR) | DCR is defined as the percentage of participants with a best overall response of CR, PR, or SD using the modified irRC per Investigator assessment. CR was defined as the disappearance of all lesions; PR was defined as a decrease in tumor area ≥ 50% relative to baseline, response must have been confirmed by a second, consecutive assessment at least 4 weeks apart; and SD was defined as any outcome not meeting the criteria for response or PD with ≥ 84 days elapsed after enrollment. | Tumor assessments were performed at week 6 (prior to initiation of pembrolizumab), week 18, and every 12 weeks thereafter until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 58.6 (1.4, 61.6) months. |
| Phase 1b: Progression-free Survival (PFS) | Progression-free survival is defined as the time from first dose to the earlier event of confirmed PD per modified irRC or death from any cause. PFS was estimated using the Kaplan-Meier method. Participants without an event were censored at their last evaluable tumor assessment. | From first dose until the end of study; median (range) time on follow-up was 70.6 (1.4, 74.5) months. |
| Phase 1b: Overall Survival (OS) | Overall survival is defined as the interval from first dose to death from any cause. OS was estimated using the Kaplan-Meier method. Participants without an event were censored at their last known alive date. | From first dose until the end of study; median (range) time on follow-up was 70.6 (1.4, 74.5) months. |
| Phase 3: Complete Response Rate Assessed Using Modified irRC-RECIST (iCRR) | Complete response rate per modified Immune-related Response Criteria (irRC) simulating RECIST 1.1 (irRC-RECIST) is defined as the percentage of participants with a best overall response of complete response assessed using the modified irRC-RECIST (iCR) evaluated by blinded independent central review. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment at least 4 weeks after the criteria were first met. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Modifications to the irRC-RECIST 1.1 included an increase in the total number of target lesions and new measurable lesions to 10 with a maximum of 5 target lesions per organ, and target lesions must have been measurable by CT or MRI only. | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
| Phase 3: Progression Free Survival Assessed Using Modified irRC-RECIST (iPFS) | PFS per modified irRC-RECIST is defined as the interval from randomization to the earlier event of progressive disease assessed by modified irRC-RECIST (iPD) evaluated by blinded independent central review, or death from any cause. iPD: Increase in tumor burden ≥ 20% and at least 5 mm absolute increase relative to nadir (minimum recorded tumor burden) confirmed by a repeat, consecutive assessment at least 4 weeks after the initial detection. Median iPFS was calculated using the Kaplan-Meier method. Participants without an event were censored at their last evaluable tumor assessment if available; otherwise on their randomization date. The primary analysis of iPFS was specified to be conducted when 256 iPFS events had occurred (data cut-off date 29 September 2020). | From randomization until the data cut-off date of 29 September 2020; median time on follow-up was 30.6 (0.6, 53.0) months in the Placebo + Pembrolizumab arm and 31.4 (0.3, 52.5) months in the Talimogene Laherparepvec + Pembrolizumab arm. |
| Phase 3: Overall Survival Excluding Stage IVM1c Participants | Overall survival is defined as the interval from randomization to death from any cause. Median OS was calculated using the Kaplan-Meier method. Participants without an event were censored at the last known alive date. | From randomization until the end of study; median (range) time on follow-up was 34.8 (0.6, 58.3) months in the Placebo + Pembrolizumab arm and 36.8 (0.3, 58.4) months in the Talimogene Laherparepvec + Pembrolizumab arm. |
| Phase 3: Objective Response Rate Assessed Using Modified RECIST 1.1 | ORR is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) assessed using modified RECIST version 1.1, evaluated by blinded independent central review. CR was defined as the disappearance of all lesions except lymph node short axis < 10 mm; PR was defined as a ≥ 30% reduction in sum of diameters in target lesions. Confirmation of CR or PR was not required. Modifications to conventional RECIST 1.1 included the following: target lesions were measurable on CT or MRI; otherwise, they were considered as nontarget lesions. A maximum of 10 target lesions was allowed with up to 5 per organ. | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
| Phase 3: Best Overall Response Assessed Using Modified RECIST 1.1 | BOR is defined as the best overall visit response up to and including the first overall visit response of PD in the following order: CR, PR, SD, non-CR/Non-PD (NN), PD or UE per modified RECIST 1.1, evaluated by BICR. CR: Disappearance of all lesions except lymph node short axis < 10 mm; PR: ≥ 30% reduction in sum of diameters in target lesions. Confirmation of CR or PR was not required; NN: Persistence of ≥ 1 non-target lesions and/or maintenance of tumor marker level above normal limits; SD: Neither sufficient shrinkage of target lesions to qualify for CR or PR nor sufficient increase to qualify for PD and ≥ 84 days from randomization; PD: Increase from nadir by ≥ 20% or ≥ 5 mm of target lesions or any new lesion; Missing: No postbaseline assessment, or assessments on or after the start of first subsequent anticancer therapy, including complete or partial removal/reduction of any target lesion which contained melanoma on pathology evaluation or pathology results were unknown. | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
| Phase 3: Durable Response Rate (DRR) Assessed Using Modified RECIST 1.1 | DRR is defined as the percentage of participants with a CR or PR per modified RECIST 1.1 evaluated by blinded independent central review, with a duration of response of ≥ 6 months. CR was defined as the disappearance of all lesions except lymph node short axis < 10 mm; PR was defined as a ≥ 30% reduction in sum of diameters in target lesions. Confirmation of CR or PR was not required. | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
| Phase 3: Duration of Response (DOR) Assessed Using Modified RECIST 1.1 | Duration of response (DOR) is defined as the time from the date of an initial response of CR or PR to the earlier of PD per modified RECIST 1.1, or death. Participants who had not ended their response at the time of analysis were censored at their last evaluable tumor assessment date before start of the first subsequent anticancer therapy. CR was defined as the disappearance of all lesions except lymph node short axis < 10 mm; PR was defined as a ≥ 30% reduction in sum of diameters in target lesions. Confirmation of CR or PR was not required. PD was defined as an increase from nadir by ≥ 20% or ≥ 5 mm absolute increase above nadir of target lesions or appearance of any new lesion. | From randomization until the data cut-off date of 29 September 2020; median time on follow-up was 30.6 (0.6, 53.0) months in the Placebo + Pembrolizumab arm and 31.4 (0.3, 52.5) months in the Talimogene Laherparepvec + Pembrolizumab arm. |
| Phase 3: Disease Control Rate (DCR) Assessed Using RECIST 1.1 | Disease control rate (DCR) per modified RECIST 1.1 is defined as the percentage of participants with a best overall response of CR, PR or SD evaluated by blinded independent central review. CR was defined as the disappearance of all lesions except lymph node short axis < 10 mm; PR was defined as a ≥ 30% reduction in sum of diameters in target lesions. Confirmation of CR or PR was not required. SD was defined as neither sufficient shrinkage of target lesions to qualify for CR or PR nor sufficient increase to qualify for PD with ≥ 84 days elapsed after randomization. | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
| Phase 3: Objective Response Rate Assessed Using Modified irRC-RECIST (iORR) | Objective response rate per modified irRC-RECIST is defined as the percentage of participants with a best overall response of iCR or partial response assessed using modified irRC-RECIST (iPR) evaluated by blinded independent central review. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment at least 4 weeks from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. iPR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation. Modifications to the irRC-RECIST 1.1 included an increase in the total number of target lesions and new measurable lesions to 10 with a maximum of 5 target lesions per organ, and target lesions must be measurable by CT or MRI only. | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
| Phase 3: Best Overall Response Assessed Using Modified irRC-RECIST | BOR is defined as the best overall visit response in the following order: iCR, iPR, stable disease per modified irRC-RECIST (iSD), iPD, or UE per modified irRC-RECIST (iUE), evaluated by BICR. iCR: Disappearance of all lesions confirmed by consecutive assessment ≥ 4 weeks from the date first documented. Reduction of any pathological lymph node to <10 mm. iPR: Decrease in tumor burden ≥ 30% relative to baseline confirmed ≥ 4 weeks after first documentation. iPD: Increase in tumor burden ≥ 20 % and at least 5 mm absolute increase relative to nadir confirmed ≥ 4 weeks from initial detection. iSD: Neither sufficient shrinkage to qualify for iCR or iPR nor sufficient increase to qualify for iPD and ≥ 84 days from randomization. Missing: No postbaseline assessment, or assessments after start of first subsequent anticancer therapy, including complete or partial removal/reduction of any target lesion which contained melanoma on pathology evaluation or pathology results were unknown. | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
| Phase 3: Durable Response Rate Assessed Using Modified irRC-RECIST (iDRR) | Durable response rate per modified irRC-RECIST is defined as the percentage of participants with a best overall response of iCR or iPR per modified irRC-RECIST evaluated by blinded independent central review with a duration of response ≥ 6 months. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment at least 4 weeks from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. iPR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation. | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
| Phase 3: Duration of Response Assessed Using Modified irRC-RECIST (iDOR) | Duration of response per modified irRC-RECIST is defined as the time from the date of an initial response of iCR or iPR that was subsequently confirmed to the earlier of iPD per modified irRC-RECIST evaluated by blinded independent central review, or death. Participants who had not ended their response at the time of analysis were censored at their last evaluable tumor assessment date before the start of the first subsequent anticancer therapy. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment at least 4 weeks from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. iPR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation. | From randomization until the data cut-off date of 29 September 2020; median time on follow-up was 30.6 (0.6, 53.0) months in the Placebo + Pembrolizumab arm and 31.4 (0.3, 52.5) months in the Talimogene Laherparepvec + Pembrolizumab arm. |
| Phase 3: Disease Control Rate Assessed Using Modified irRC-RECIST (iDCR) | Disease control rate per modified irRC-RECIST is defined as the percentage of participants with a best overall response of iCR, iCR, or iSD assessed using modified irRC-RECIST evaluated by blinded independent central review. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment at least 4 weeks from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. iPR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation. iSD: Neither sufficient shrinkage to qualify for iCR or iPR nor sufficient increase to qualify for iPD with ≥ 84 days elapsed after randomization. | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
| Phase 3: Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL) Score | The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status/quality of life scale, 5 functional scales, and 9 symptom scales/items. The global health/QoL scale consists of 2 questions that ask participants to rate their overall health and overall quality of life during the past week on a scale from 1 (very poor) to 7 (excellent). The GHS/QoL subscale score was derived as the mean of each score then transformed to a scale from 0 to 100 where higher scores represent a better health status and a positive change from baseline indicates improvement. The overall change from baseline (calculated from all on-treatment visits) was calculated using a restricted maximum likelihood-based mixed model for repeated measures (MMRM) (see model details in statistical analysis section). | Baseline and day 1 of weeks 3, 6, 9, 12, then every 6 weeks until end of study treatment; median (range) duration of treatment was 39.0 (0.1, 107.3) weeks in Placebo + Pembrolizumab and 54.1 (0.1, 109.6) weeks in Talimogene Laherparepvec + Pembrolizumab. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a clinical trial subject, including worsening of a pre-existing medical condition. The event does not necessarily have a causal relationship with study treatment. TEAEs include AEs from the first dose of study drug to 30 days after the last dose. A serious adverse event (SAE) is an AE that met at least 1 of the following criteria:
AEs were graded for severity using CTCAE version 4.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Fatal. | From first dose to 30 days after last dose (90 days for SAEs); median (range) duration was 48 (5.1, 110.1) weeks in Phase 1b, 39 (0.1, 107.3) weeks in Placebo + Pembrolizumab and 56 (0.1, 109.6) weeks in Phase 3 Talimogene Laherparepvec + Pembrolizumab. |
| Mobile |
| Alabama |
| 36608 |
| United States |
| Research Site | Beverly Hills | California | 90211 | United States |
| Research Site | Duarte | California | 91010 | United States |
| Research Site | Encinitas | California | 92024 | United States |
| Research Site | La Jolla | California | 92037 | United States |
| Research Site | Los Angeles | California | 90024 | United States |
| Research Site | Los Angeles | California | 90025 | United States |
| Research Site | Riverside | California | 92505 | United States |
| Research Site | San Francisco | California | 94115 | United States |
| Research Site | San Francisco | California | 94117 | United States |
| Research Site | Santa Monica | California | 90404 | United States |
| Research Site | Miami | Florida | 33136 | United States |
| Research Site | Miami Beach | Florida | 33140 | United States |
| Research Site | Orlando | Florida | 32806 | United States |
| Research Site | Atlanta | Georgia | 30322 | United States |
| Research Site | Chicago | Illinois | 60611 | United States |
| Research Site | Chicago | Illinois | 60637 | United States |
| Research Site | Louisville | Kentucky | 40202 | United States |
| Research Site | Baltimore | Maryland | 21237 | United States |
| Research Site | Boston | Massachusetts | 02215 | United States |
| Research Site | Detroit | Michigan | 48201 | United States |
| Research Site | Fridley | Minnesota | 55432 | United States |
| Research Site | St Louis | Missouri | 63110-1093 | United States |
| Research Site | Hackensack | New Jersey | 07601 | United States |
| Research Site | Buffalo | New York | 14263 | United States |
| Research Site | New York | New York | 10016 | United States |
| Research Site | New York | New York | 10032 | United States |
| Research Site | New York | New York | 10065 | United States |
| Research Site | Cincinnati | Ohio | 45209 | United States |
| Research Site | Cleveland | Ohio | 44195 | United States |
| Research Site | Philadelphia | Pennsylvania | 19107 | United States |
| Research Site | Philadelphia | Pennsylvania | 19111 | United States |
| Research Site | Pittsburgh | Pennsylvania | 15232 | United States |
| Research Site | Germantown | Tennessee | 38138 | United States |
| Research Site | Knoxville | Tennessee | 37920 | United States |
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| Research Site | Dallas | Texas | 75246 | United States |
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| Research Site | Salt Lake City | Utah | 84112 | United States |
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| Research Site | North Sydney | New South Wales | 2060 | Australia |
| Research Site | Waratah | New South Wales | 2298 | Australia |
| Research Site | Wollongong | New South Wales | 2500 | Australia |
| Research Site | Southport | Queensland | 4215 | Australia |
| Research Site | Woolloongabba | Queensland | 4102 | Australia |
| Research Site | Woodville South | South Australia | 5011 | Australia |
| Research Site | Geelong | Victoria | 3220 | Australia |
| Research Site | Heidelberg | Victoria | 3084 | Australia |
| Research Site | Melbourne | Victoria | 3000 | Australia |
| Research Site | Prahran | Victoria | 3181 | Australia |
| Research Site | Murdoch | Western Australia | 6150 | Australia |
| Research Site | Graz | 8036 | Austria |
| Research Site | Innsbruck | 6020 | Austria |
| Research Site | Salzburg | 5020 | Austria |
| Research Site | Vienna | 1090 | Austria |
| Research Site | Brussels | 1200 | Belgium |
| Research Site | Liège | 4000 | Belgium |
| Research Site | Edmonton | Alberta | T6G 1Z2 | Canada |
| Research Site | Kingston | Ontario | K7L 2V7 | Canada |
| Research Site | London | Ontario | N6A 4L6 | Canada |
| Research Site | Ottawa | Ontario | K1H 8L6 | Canada |
| Research Site | Toronto | Ontario | M5G 2M9 | Canada |
| Research Site | Montreal | Quebec | H3T 1E2 | Canada |
| Research Site | Québec | Quebec | G1R 2J6 | Canada |
| Research Site | Brno | 656 53 | Czechia |
| Research Site | Olomouc | 775 20 | Czechia |
| Research Site | Ostrava-Poruba | 708 52 | Czechia |
| Research Site | Prague | 100 34 | Czechia |
| Research Site | Prague | 128 08 | Czechia |
| Research Site | Prague | 180 81 | Czechia |
| Research Site | Helsinki | 00290 | Finland |
| Research Site | Bordeaux | 33075 | France |
| Research Site | Grenoble | 38043 | France |
| Research Site | Lille | 59037 | France |
| Research Site | Lyon | 69373 | France |
| Research Site | Marseille | 13385 | France |
| Research Site | Nantes | 44093 | France |
| Research Site | Paris | 75010 | France |
| Research Site | Pierre-Bénite | 69495 | France |
| Research Site | Toulouse | 31059 | France |
| Research Site | Vandœuvre-lès-Nancy | 54511 | France |
| Research Site | Berlin | 10117 | Germany |
| Research Site | Dresden | 01307 | Germany |
| Research Site | Erlangen | 91054 | Germany |
| Research Site | Essen | 45147 | Germany |
| Research Site | Hanover | 30625 | Germany |
| Research Site | Heidelberg | 69120 | Germany |
| Research Site | Kiel | 24105 | Germany |
| Research Site | Leipzig | 04103 | Germany |
| Research Site | Mainz | 55131 | Germany |
| Research Site | Mannheim | 68167 | Germany |
| Research Site | München | 80337 | Germany |
| Research Site | Regensburg | 93053 | Germany |
| Research Site | Tübingen | 72076 | Germany |
| Research Site | Würzburg | 97080 | Germany |
| Research Site | Athens | 11527 | Greece |
| Research Site | Athens | 18547 | Greece |
| Research Site | Heraklion - Crete | 71110 | Greece |
| Research Site | Ioannina | 45500 | Greece |
| Research Site | Thessaloniki | 54622 | Greece |
| Research Site | Budapest | 1122 | Hungary |
| Research Site | Pécs | 7632 | Hungary |
| Research Site | Szeged | 6720 | Hungary |
| Research Site | Bergamo | 24127 | Italy |
| Research Site | Brescia | 25123 | Italy |
| Research Site | Meldola FC | 47014 | Italy |
| Research Site | Milan | 20133 | Italy |
| Research Site | Milan | 20141 | Italy |
| Research Site | Siena | 53100 | Italy |
| Research Site | Amsterdam | 1066 CX | Netherlands |
| Research Site | Amsterdam | 1081 HV | Netherlands |
| Research Site | Groningen | 9713 GZ | Netherlands |
| Research Site | Nijmegen | 6525 GA | Netherlands |
| Research Site | Bielsko-Biala | 43-300 | Poland |
| Research Site | Bydgoszcz | 85-796 | Poland |
| Research Site | Gdansk | 80-952 | Poland |
| Research Site | Konin | 62-500 | Poland |
| Research Site | Krakow | 31-501 | Poland |
| Research Site | Poznan | 60-848 | Poland |
| Research Site | Poznan | 61-866 | Poland |
| Research Site | Szczecin | 71-730 | Poland |
| Research Site | Warsaw | 02-781 | Poland |
| Research Site | Wroclaw | 50-368 | Poland |
| Research Site | Almada | 2801-951 | Portugal |
| Research Site | Lisbon | 1099-023 | Portugal |
| Research Site | Lisbon | 1649-035 | Portugal |
| Research Site | Porto | 4200-072 | Portugal |
| Research Site | Moscow | 115478 | Russia |
| Research Site | Saint Petersburg | 197758 | Russia |
| Research Site | Groenkloof | Gauteng | 0181 | South Africa |
| Research Site | Johannesburg | Gauteng | 2196 | South Africa |
| Research Site | Parktown | Gauteng | 2193 | South Africa |
| Research Site | Kraaifontein | 7570 | South Africa |
| Research Site | Pretoria | 0002 | South Africa |
| Research Site | Pretoria | 0081 | South Africa |
| Research Site | Seoul | 03722 | South Korea |
| Research Site | Seoul | 05505 | South Korea |
| Research Site | Donostia / San Sebastian | Basque Country | 20014 | Spain |
| Research Site | Badalona | Catalonia | 08916 | Spain |
| Research Site | Barcelona | Catalonia | 08036 | Spain |
| Research Site | Pamplona | Navarre | 31008 | Spain |
| Research Site | Valencia | Valencia | 46014 | Spain |
| Research Site | Madrid | 28009 | Spain |
| Research Site | Madrid | 28046 | Spain |
| Research Site | Madrid | 28050 | Spain |
| Research Site | Bellinzona | 6500 | Switzerland |
| Research Site | Bern | 3010 | Switzerland |
| Research Site | Geneva | 1211 | Switzerland |
| Research Site | Lausanne | 1011 | Switzerland |
| Research Site | Zurich | 8091 | Switzerland |
| Research Site | Birmingham | B15 2TH | United Kingdom |
| Research Site | Guildford | GU2 7XX | United Kingdom |
| Research Site | Leeds | LS9 7TF | United Kingdom |
| Research Site | Leicester | LE1 5WW | United Kingdom |
| Research Site | London | SE1 9RT | United Kingdom |
| Research Site | London | SW3 6JJ | United Kingdom |
| Research Site | Manchester | M20 4BX | United Kingdom |
| Research Site | Oxford | OX3 7LJ | United Kingdom |
| Research Site | Preston | PR2 9HT | United Kingdom |
| Research Site | Southampton | SO16 6YD | United Kingdom |
| Background |
| Dummer R, Hoeller C, Gruter IP, Michielin O. Combining talimogene laherparepvec with immunotherapies in melanoma and other solid tumors. Cancer Immunol Immunother. 2017 Jun;66(6):683-695. doi: 10.1007/s00262-017-1967-1. Epub 2017 Feb 25. |
| 35998300 | Background | Chesney JA, Ribas A, Long GV, Kirkwood JM, Dummer R, Puzanov I, Hoeller C, Gajewski TF, Gutzmer R, Rutkowski P, Demidov L, Arenberger P, Shin SJ, Ferrucci PF, Haydon A, Hyngstrom J, van Thienen JV, Haferkamp S, Guilera JM, Rapoport BL, VanderWalde A, Diede SJ, Anderson JR, Treichel S, Chan EL, Bhatta S, Gansert J, Hodi FS, Gogas H. Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma. J Clin Oncol. 2023 Jan 20;41(3):528-540. doi: 10.1200/JCO.22.00343. Epub 2022 Aug 23. |
| 29896663 | Derived | Watanabe D, Goshima F. Oncolytic Virotherapy by HSV. Adv Exp Med Biol. 2018;1045:63-84. doi: 10.1007/978-981-10-7230-7_4. |
| FG001 | Phase 3: Placebo + Pembrolizumab | Participants received up to 4 mL placebo to talimogene laherparepvec by intralesional injection on day 1 of week 0. Subsequent doses of placebo (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, complete response per modified Immune-related Response Criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST) (iCR), confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of placebo, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
| FG002 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
| Received Talimogene Laherparepvec/Placebo |
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| Received Pembrolizumab |
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| COMPLETED |
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| NOT COMPLETED |
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All enrolled participants
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Phase 1b: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ plaque-forming units (PFU)/mL by intralesional injection on day 1 of week 1. Subsequent doses of talimogene laherparepvec at up to 4 mL of 10⁸ PFU/mL began 3 weeks after the first dose and were administered every 2 weeks until disappearance of injectable lesions, complete response (CR), confirmed disease progression (PD) per modified Immune-related Response Criteria (irRC), intolerance of study treatment, 24 months from the date of the first dose of pembrolizumab, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 2 weeks starting at the time of the third dose of talimogene laherparepvec (week 6) until confirmed PD per modified irRC, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
| BG001 | Phase 3: Placebo + Pembrolizumab | Participants received up to 4 mL placebo to talimogene laherparepvec by intralesional injection on day 1 of week 0. Subsequent doses of placebo (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, complete response per modified Immune-related Response Criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST) (iCR), confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of placebo, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
| BG002 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
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| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | |||||
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| Age, Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Disease Stage per the American Joint Committee on Cancer (AJCC) 7th Edition | Stage IIIB: Ulcerated lesion and 1 lymph node or 2-3 nodes with micrometastasis, or any-depth lesion with no ulceration, and 1 lymph node or 2-3 nodes with macrometastasis; Stage IIIC: Ulcerated lesion and 1 lymph node with macrometastasis; 2-3 nodes with macrometastasis or ≥4 metastatic lymph nodes, matted lymph nodes, or in-transit met(s)/satellite(s); Stage IV: M1a: Spread to skin, subcutaneous tissue, or lymph nodes; normal lactate dehydrogenase (LDH) level; M1b: Spread to lungs, normal LDH; M1c: Spread to all other visceral organs, normal LDH or any distant disease with elevated LDH. | Count of Participants | Participants |
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| Prior Serine/Threonine Protein Kinase B-Raf (BRAF) Inhibitor Therapy | Prior BRAF inhibitor therapy was not collected in Phase 1b | Count of Participants | Participants |
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| Programmed Cell Death-1 Ligand 1 (PD-L1) Status | PD-L1 expression in tumor cells was assessed at a central laboratory using a clinical trial immunohistochemistry assay (22C3 antibody) and scored on a unique melanoma (MEL) scale of 0 to 5; a score ≥ 2 (membranous staining in ≥ 1% of cells within tumor nests, including neoplastic cells and intercalated and contiguous immune cells) was considered positive. | Count of Participants | Participants |
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| BRAF V600 Mutation Status | Mutation status of v-raf murine sarcoma viral oncogene homolog B1 (BRAF) gene was based on a gene mutation that results in an amino acid substitution from valine (V) to glutamic acid (E) at codon 600 (V600E) and/or a substitution from valine to lysine (K) (V600K). | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||
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| Primary | Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs) | A DLT was defined as any toxicity related to study drug which met any of the following criteria based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0:
| The DLT analysis set included DLT-evaluable participants enrolled in Phase 1b who had the opportunity to be on treatment for at least 6 weeks from the initial dose of pembrolizumab and received at least 2 doses of talimogene laherparepvec and 2 doses of pembrolizumab in combination (ie, on the same day), or those who otherwise experienced a DLT within 6 weeks after starting the combination therapy. | Posted | Count of Participants | Participants | The DLT evaluation period was 6 weeks from the initial administration of pembrolizumab (week 6 to 12). |
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| Primary | Phase 3: Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) Assessed Using Modified RECIST 1.1 | PFS per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 is defined as the interval from randomization to the earlier event of progressive disease (PD) per modified RECIST 1.1 or death from any cause. PD: Increase in size of target lesions from nadir by ≥ 20% and ≥ 5 mm absolute increase above nadir, or the appearance of a new lesion. Median PFS was calculated using the Kaplan-Meier method. Participants without an event were censored at their last evaluable tumor assessment if available; otherwise on their randomization date. The primary analysis of PFS was specified to be conducted when 407 PFS events had occurred (data cut-off date 02 March 2020). | All participants randomized in Phase 3. | Posted | Median | 95% Confidence Interval | months | From randomization until the data-cut-off date of 02 March 2020; median (range) time on follow-up was 25.5 (0.6, 44.7) months in the Placebo + Pembrolizumab arm and 25.6 (0.3, 45.8) months in the Talimogene Laherparepvec + Pembrolizumab arm. |
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| Primary | Phase 3: Overall Survival | Overall survival (OS) is defined as the interval from randomization to death from any cause. Median overall survival was calculated using the Kaplan-Meier method. Participants without an event were censored at their last known alive date. | All participants randomized in Phase 3 | Posted | Median | 95% Confidence Interval | months | From randomization until the end of study; median (range) time on follow-up was 34.8 (0.6, 58.3) months in the Placebo + Pembrolizumab arm and 36.8 (0.3, 58.4) months in the Talimogene Laherparepvec + Pembrolizumab arm. |
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| Secondary | Phase 1b: Objective Response Rate (ORR) | ORR is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) using the modified Immune-related Response Criteria (irRC), by Investigator assessment. CR was defined as the disappearance of all lesions; PR was defined as a decrease in tumor area ≥ 50% relative to baseline, response must have been confirmed by a second, consecutive assessment at least 4 weeks apart. Radiographic imaging for assessment of lesions was performed using computed tomography (CT), positron emission tomography (PET), magnetic resonance imaging (MRI), or ultrasound. Clinical measurement of cutaneous, subcutaneous, and palpable nodal tumor lesions was conducted with calipers. | All participants enrolled in Phase 1b who received ≥ 1 dose of talimogene laherparepvec or pembrolizumab. Participants with no post-baseline tumor assessments were counted as non-responders. | Posted | Number | 95% Confidence Interval | percentage of participants | Tumor assessments were performed at week 6 (prior to initiation of pembrolizumab), week 18, and every 12 weeks thereafter until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 58.6 (1.4, 61.6) months. |
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| Secondary | Phase 1b: Best Overall Response (BOR) | Best overall response is defined as the best overall visit response in the following order: CR, PR, stable disease (SD), progressive disease (PD), or unevaluable (UE), based on investigator assessment using the modified irRC up to the start of any subsequent anti-cancer therapy. CR was defined as the disappearance of all lesions; PR was defined as a decrease in tumor area ≥ 50% relative to baseline; PD was defined as an increase in tumor area ≥ 25% relative to nadir; and SD was defined as any outcome not meeting the criteria for response or PD with ≥ 77 days elapsed after enrollment. Responses and PD must have been confirmed by a second, consecutive assessment at least 4 weeks apart. | All participants enrolled in Phase 1b who received ≥ 1 dose of talimogene laherparepvec or pembrolizumab. | Posted | Count of Participants | Participants | Tumor assessments were performed at week 6 (prior to initiation of pembrolizumab), week 18, and every 12 weeks thereafter until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 58.6 (1.4, 61.6) months. |
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| Secondary | Phase 1b: Durable Response Rate (DRR) | DRR is defined as the percentage of participants with a best overall response of CR or PR using the modified irRC per Investigator assessment with a duration of response of at least 6 months. CR was defined as the disappearance of all lesions; PR was defined as a decrease in tumor area ≥ 50% relative to baseline, response must have been confirmed by a second, consecutive assessment at least 4 weeks apart. | All participants enrolled in Phase 1b who received ≥ 1 dose of talimogene laherparepvec or pembrolizumab. | Posted | Number | 95% Confidence Interval | percentage of participants | Tumor assessments were performed at week 6 (prior to initiation of pembrolizumab), week 18, and every 12 weeks thereafter until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 58.6 (1.4, 61.6) months. |
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| Secondary | Phase 1b: Duration of Response (DOR) | Duration of response (DOR) is defined as the time from the date of an initial response (CR or PR) that is subsequently confirmed to the earlier of confirmed PD or death. Participants who had not ended their response at the time of analysis were censored at their last evaluable tumor assessment before start of the first subsequent anticancer therapy. CR was defined as the disappearance of all lesions; PR was defined as a decrease in tumor area ≥ 50% relative to baseline; PD was defined as an increase in tumor area ≥ 25% relative to nadir. Response and PD must have been confirmed by a second, consecutive assessment at least 4 weeks apart. | All participants enrolled in Phase 1b who received ≥ 1 dose of talimogene laherparepvec or pembrolizumab with a CR or PR. | Posted | Median | 95% Confidence Interval | months | Tumor assessments were performed at week 6 (prior to initiation of pembrolizumab), week 18, and every 12 weeks thereafter until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 58.6 (1.4, 61.6) months. |
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| Secondary | Phase 1b: Disease Control Rate (DCR) | DCR is defined as the percentage of participants with a best overall response of CR, PR, or SD using the modified irRC per Investigator assessment. CR was defined as the disappearance of all lesions; PR was defined as a decrease in tumor area ≥ 50% relative to baseline, response must have been confirmed by a second, consecutive assessment at least 4 weeks apart; and SD was defined as any outcome not meeting the criteria for response or PD with ≥ 84 days elapsed after enrollment. | All participants enrolled in Phase 1b who received ≥ 1 dose of talimogene laherparepvec or pembrolizumab. | Posted | Number | 95% Confidence Interval | percentage of participants | Tumor assessments were performed at week 6 (prior to initiation of pembrolizumab), week 18, and every 12 weeks thereafter until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 58.6 (1.4, 61.6) months. |
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| Secondary | Phase 1b: Progression-free Survival (PFS) | Progression-free survival is defined as the time from first dose to the earlier event of confirmed PD per modified irRC or death from any cause. PFS was estimated using the Kaplan-Meier method. Participants without an event were censored at their last evaluable tumor assessment. | All participants enrolled in Phase 1b who received ≥ 1 dose of talimogene laherparepvec or pembrolizumab. | Posted | Median | 95% Confidence Interval | months | From first dose until the end of study; median (range) time on follow-up was 70.6 (1.4, 74.5) months. |
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| Secondary | Phase 1b: Overall Survival (OS) | Overall survival is defined as the interval from first dose to death from any cause. OS was estimated using the Kaplan-Meier method. Participants without an event were censored at their last known alive date. | All participants enrolled in Phase 1b who received ≥ 1 dose of talimogene laherparepvec or pembrolizumab | Posted | Median | 95% Confidence Interval | months | From first dose until the end of study; median (range) time on follow-up was 70.6 (1.4, 74.5) months. |
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| Secondary | Phase 3: Complete Response Rate Assessed Using Modified irRC-RECIST (iCRR) | Complete response rate per modified Immune-related Response Criteria (irRC) simulating RECIST 1.1 (irRC-RECIST) is defined as the percentage of participants with a best overall response of complete response assessed using the modified irRC-RECIST (iCR) evaluated by blinded independent central review. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment at least 4 weeks after the criteria were first met. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Modifications to the irRC-RECIST 1.1 included an increase in the total number of target lesions and new measurable lesions to 10 with a maximum of 5 target lesions per organ, and target lesions must have been measurable by CT or MRI only. | All participants randomized in Phase 3 | Posted | Number | 95% Confidence Interval | percentage of participants | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
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| Secondary | Phase 3: Progression Free Survival Assessed Using Modified irRC-RECIST (iPFS) | PFS per modified irRC-RECIST is defined as the interval from randomization to the earlier event of progressive disease assessed by modified irRC-RECIST (iPD) evaluated by blinded independent central review, or death from any cause. iPD: Increase in tumor burden ≥ 20% and at least 5 mm absolute increase relative to nadir (minimum recorded tumor burden) confirmed by a repeat, consecutive assessment at least 4 weeks after the initial detection. Median iPFS was calculated using the Kaplan-Meier method. Participants without an event were censored at their last evaluable tumor assessment if available; otherwise on their randomization date. The primary analysis of iPFS was specified to be conducted when 256 iPFS events had occurred (data cut-off date 29 September 2020). | All participants randomized in Phase 3 | Posted | Median | 95% Confidence Interval | months | From randomization until the data cut-off date of 29 September 2020; median time on follow-up was 30.6 (0.6, 53.0) months in the Placebo + Pembrolizumab arm and 31.4 (0.3, 52.5) months in the Talimogene Laherparepvec + Pembrolizumab arm. |
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| Secondary | Phase 3: Overall Survival Excluding Stage IVM1c Participants | Overall survival is defined as the interval from randomization to death from any cause. Median OS was calculated using the Kaplan-Meier method. Participants without an event were censored at the last known alive date. | Participants randomized in Phase 3 with stage IIIB to IVM1a/b. | Posted | Median | 95% Confidence Interval | months | From randomization until the end of study; median (range) time on follow-up was 34.8 (0.6, 58.3) months in the Placebo + Pembrolizumab arm and 36.8 (0.3, 58.4) months in the Talimogene Laherparepvec + Pembrolizumab arm. |
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| Secondary | Phase 3: Objective Response Rate Assessed Using Modified RECIST 1.1 | ORR is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) assessed using modified RECIST version 1.1, evaluated by blinded independent central review. CR was defined as the disappearance of all lesions except lymph node short axis < 10 mm; PR was defined as a ≥ 30% reduction in sum of diameters in target lesions. Confirmation of CR or PR was not required. Modifications to conventional RECIST 1.1 included the following: target lesions were measurable on CT or MRI; otherwise, they were considered as nontarget lesions. A maximum of 10 target lesions was allowed with up to 5 per organ. | All participants randomized in Phase 3; Participants with no post-baseline tumor assessments were counted as non-responders. | Posted | Number | 95% Confidence Interval | percentage of participants | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
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| Secondary | Phase 3: Best Overall Response Assessed Using Modified RECIST 1.1 | BOR is defined as the best overall visit response up to and including the first overall visit response of PD in the following order: CR, PR, SD, non-CR/Non-PD (NN), PD or UE per modified RECIST 1.1, evaluated by BICR. CR: Disappearance of all lesions except lymph node short axis < 10 mm; PR: ≥ 30% reduction in sum of diameters in target lesions. Confirmation of CR or PR was not required; NN: Persistence of ≥ 1 non-target lesions and/or maintenance of tumor marker level above normal limits; SD: Neither sufficient shrinkage of target lesions to qualify for CR or PR nor sufficient increase to qualify for PD and ≥ 84 days from randomization; PD: Increase from nadir by ≥ 20% or ≥ 5 mm of target lesions or any new lesion; Missing: No postbaseline assessment, or assessments on or after the start of first subsequent anticancer therapy, including complete or partial removal/reduction of any target lesion which contained melanoma on pathology evaluation or pathology results were unknown. | All participants randomized in Phase 3 | Posted | Count of Participants | Participants | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
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| Secondary | Phase 3: Durable Response Rate (DRR) Assessed Using Modified RECIST 1.1 | DRR is defined as the percentage of participants with a CR or PR per modified RECIST 1.1 evaluated by blinded independent central review, with a duration of response of ≥ 6 months. CR was defined as the disappearance of all lesions except lymph node short axis < 10 mm; PR was defined as a ≥ 30% reduction in sum of diameters in target lesions. Confirmation of CR or PR was not required. | All participants randomized in Phase 3 | Posted | Number | 95% Confidence Interval | percentage of participants | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
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| Secondary | Phase 3: Duration of Response (DOR) Assessed Using Modified RECIST 1.1 | Duration of response (DOR) is defined as the time from the date of an initial response of CR or PR to the earlier of PD per modified RECIST 1.1, or death. Participants who had not ended their response at the time of analysis were censored at their last evaluable tumor assessment date before start of the first subsequent anticancer therapy. CR was defined as the disappearance of all lesions except lymph node short axis < 10 mm; PR was defined as a ≥ 30% reduction in sum of diameters in target lesions. Confirmation of CR or PR was not required. PD was defined as an increase from nadir by ≥ 20% or ≥ 5 mm absolute increase above nadir of target lesions or appearance of any new lesion. | Participants randomized in Phase 3 with a CR or PR per modified RECIST. | Posted | Median | 95% Confidence Interval | months | From randomization until the data cut-off date of 29 September 2020; median time on follow-up was 30.6 (0.6, 53.0) months in the Placebo + Pembrolizumab arm and 31.4 (0.3, 52.5) months in the Talimogene Laherparepvec + Pembrolizumab arm. |
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| Secondary | Phase 3: Disease Control Rate (DCR) Assessed Using RECIST 1.1 | Disease control rate (DCR) per modified RECIST 1.1 is defined as the percentage of participants with a best overall response of CR, PR or SD evaluated by blinded independent central review. CR was defined as the disappearance of all lesions except lymph node short axis < 10 mm; PR was defined as a ≥ 30% reduction in sum of diameters in target lesions. Confirmation of CR or PR was not required. SD was defined as neither sufficient shrinkage of target lesions to qualify for CR or PR nor sufficient increase to qualify for PD with ≥ 84 days elapsed after randomization. | All participants randomized in Phase 3 | Posted | Number | 95% Confidence Interval | percentage of participants | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
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| Secondary | Phase 3: Objective Response Rate Assessed Using Modified irRC-RECIST (iORR) | Objective response rate per modified irRC-RECIST is defined as the percentage of participants with a best overall response of iCR or partial response assessed using modified irRC-RECIST (iPR) evaluated by blinded independent central review. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment at least 4 weeks from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. iPR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation. Modifications to the irRC-RECIST 1.1 included an increase in the total number of target lesions and new measurable lesions to 10 with a maximum of 5 target lesions per organ, and target lesions must be measurable by CT or MRI only. | All participants randomized in Phase 3 | Posted | Number | 95% Confidence Interval | percentage of participants | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
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| Secondary | Phase 3: Best Overall Response Assessed Using Modified irRC-RECIST | BOR is defined as the best overall visit response in the following order: iCR, iPR, stable disease per modified irRC-RECIST (iSD), iPD, or UE per modified irRC-RECIST (iUE), evaluated by BICR. iCR: Disappearance of all lesions confirmed by consecutive assessment ≥ 4 weeks from the date first documented. Reduction of any pathological lymph node to <10 mm. iPR: Decrease in tumor burden ≥ 30% relative to baseline confirmed ≥ 4 weeks after first documentation. iPD: Increase in tumor burden ≥ 20 % and at least 5 mm absolute increase relative to nadir confirmed ≥ 4 weeks from initial detection. iSD: Neither sufficient shrinkage to qualify for iCR or iPR nor sufficient increase to qualify for iPD and ≥ 84 days from randomization. Missing: No postbaseline assessment, or assessments after start of first subsequent anticancer therapy, including complete or partial removal/reduction of any target lesion which contained melanoma on pathology evaluation or pathology results were unknown. | All participants randomized in Phase 3 | Posted | Count of Participants | Participants | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
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| Secondary | Phase 3: Durable Response Rate Assessed Using Modified irRC-RECIST (iDRR) | Durable response rate per modified irRC-RECIST is defined as the percentage of participants with a best overall response of iCR or iPR per modified irRC-RECIST evaluated by blinded independent central review with a duration of response ≥ 6 months. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment at least 4 weeks from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. iPR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation. | All participants randomized in Phase 3 | Posted | Number | 95% Confidence Interval | percentage of participants | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
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| Secondary | Phase 3: Duration of Response Assessed Using Modified irRC-RECIST (iDOR) | Duration of response per modified irRC-RECIST is defined as the time from the date of an initial response of iCR or iPR that was subsequently confirmed to the earlier of iPD per modified irRC-RECIST evaluated by blinded independent central review, or death. Participants who had not ended their response at the time of analysis were censored at their last evaluable tumor assessment date before the start of the first subsequent anticancer therapy. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment at least 4 weeks from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. iPR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation. | Participants randomized in Phase 3 with a iCR or iPR per modified irRC-RECIST. | Posted | Median | 95% Confidence Interval | months | From randomization until the data cut-off date of 29 September 2020; median time on follow-up was 30.6 (0.6, 53.0) months in the Placebo + Pembrolizumab arm and 31.4 (0.3, 52.5) months in the Talimogene Laherparepvec + Pembrolizumab arm. |
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| Secondary | Phase 3: Disease Control Rate Assessed Using Modified irRC-RECIST (iDCR) | Disease control rate per modified irRC-RECIST is defined as the percentage of participants with a best overall response of iCR, iCR, or iSD assessed using modified irRC-RECIST evaluated by blinded independent central review. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment at least 4 weeks from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. iPR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation. iSD: Neither sufficient shrinkage to qualify for iCR or iPR nor sufficient increase to qualify for iPD with ≥ 84 days elapsed after randomization. | All participants randomized in Phase 3 | Posted | Number | 95% Confidence Interval | percentage of participants | Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively. |
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| Secondary | Phase 3: Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL) Score | The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status/quality of life scale, 5 functional scales, and 9 symptom scales/items. The global health/QoL scale consists of 2 questions that ask participants to rate their overall health and overall quality of life during the past week on a scale from 1 (very poor) to 7 (excellent). The GHS/QoL subscale score was derived as the mean of each score then transformed to a scale from 0 to 100 where higher scores represent a better health status and a positive change from baseline indicates improvement. The overall change from baseline (calculated from all on-treatment visits) was calculated using a restricted maximum likelihood-based mixed model for repeated measures (MMRM) (see model details in statistical analysis section). | Participants randomized in Phase 3 who received at least one dose of study therapy and had both a baseline and at least one on-treatment assessment. | Posted | Least Squares Mean | Standard Error | score on a scale | Baseline and day 1 of weeks 3, 6, 9, 12, then every 6 weeks until end of study treatment; median (range) duration of treatment was 39.0 (0.1, 107.3) weeks in Placebo + Pembrolizumab and 54.1 (0.1, 109.6) weeks in Talimogene Laherparepvec + Pembrolizumab. |
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| Secondary | Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) is any untoward medical occurrence in a clinical trial subject, including worsening of a pre-existing medical condition. The event does not necessarily have a causal relationship with study treatment. TEAEs include AEs from the first dose of study drug to 30 days after the last dose. A serious adverse event (SAE) is an AE that met at least 1 of the following criteria:
AEs were graded for severity using CTCAE version 4.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Fatal. | All participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab. One participant who was randomized in Phase 3 to receive placebo received talimogene laherparepvec; thus, the Safety Analysis Set consisted of 344 participants in the Talimogene Laherparepvec + Pembrolizumab group and 344 participants in the Placebo + Pembrolizumab group. | Posted | Count of Participants | Participants | From first dose to 30 days after last dose (90 days for SAEs); median (range) duration was 48 (5.1, 110.1) weeks in Phase 1b, 39 (0.1, 107.3) weeks in Placebo + Pembrolizumab and 56 (0.1, 109.6) weeks in Phase 3 Talimogene Laherparepvec + Pembrolizumab. |
|
All-cause mortality: From enrollment (Phase 1b) or randomization (Phase 3) to end of study, up to 75 months in Phase 1b and 58 months in Phase 3. SAEs: From first dose of study drug to 90 days after last dose or 30 days after last dose if new anticancer therapy was started. AEs: From first dose to 30 days after last dose; median (range) duration of exposure was 48 (5.1, 110) weeks in Phase 1b, 39 (0.1, 107) weeks in Placebo + Pembrolizumab and 56 (0.1, 110) weeks in T-VEC + Pembrolizumab arm.
All-cause mortality is reported for all enrolled (Phase 1b) or randomized (Phase 3) participants.
Adverse events are reported for all participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab.
One participant who was randomized in Phase 3 to receive placebo received talimogene laherparepvec; thus, the Safety Analysis Set consisted of 344 participants in the talimogene laherparepvec + pembrolizumab group and 344 participants in the placebo + pembrolizumab group.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Phase 1b: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ plaque-forming units (PFU)/mL by intralesional injection on day 1 of week 1. Subsequent doses of talimogene laherparepvec at up to 4 mL of 10⁸ PFU/mL began 3 weeks after the first dose and were administered every 2 weeks until disappearance of injectable lesions, complete response (CR), confirmed disease progression (PD) per modified Immune-related Response Criteria (irRC), intolerance of study treatment, 24 months from the date of the first dose of pembrolizumab, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 2 weeks starting at the time of the third dose of talimogene laherparepvec (week 6) until confirmed PD per modified irRC, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. | 6 | 21 | 8 | 21 | 21 | 21 |
| EG001 | Phase 3: Placebo + Pembrolizumab | Participants received up to 4 mL placebo to talimogene laherparepvec by intralesional injection on day 1 of week 0. Subsequent doses of placebo (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, complete response per modified Immune-related Response Criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST) (iCR), confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of placebo, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. | 156 | 346 | 141 | 344 | 305 | 344 |
| EG002 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. | 146 | 346 | 154 | 344 | 317 | 344 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
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| Anaemia of malignant disease | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
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| Febrile neutropenia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
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| Granulomatous lymphadenitis | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
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| Lymph node pain | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
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| Lymphadenopathy | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
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| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
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| Acute coronary syndrome | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Acute myocardial infarction | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Angina pectoris | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Atrial flutter | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Atrioventricular block second degree | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Cardiac arrest | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Cardiac failure | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Cardiac failure acute | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Cardiac failure congestive | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Cardiogenic shock | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Left ventricular failure | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Mitral valve prolapse | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Myocardial infarction | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Myocarditis | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Supraventricular tachycardia | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
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| Vertigo | Ear and labyrinth disorders | MedDRA 23.1 | Systematic Assessment |
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| Addison's disease | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
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| Adrenal insufficiency | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
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| Adrenocortical insufficiency acute | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
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| Endocrine disorder | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
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| Hyperthyroidism | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
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| Hypophysitis | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
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| Hypopituitarism | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
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| Lymphocytic hypophysitis | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
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| Thyroid mass | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Thyroiditis | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
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| Papilloedema | Eye disorders | MedDRA 23.1 | Systematic Assessment |
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| Retinal oedema | Eye disorders | MedDRA 23.1 | Systematic Assessment |
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| Uveitis | Eye disorders | MedDRA 23.1 | Systematic Assessment |
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| Abdominal pain | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Abdominal pain upper | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Ascites | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Autoimmune colitis | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Colitis | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Constipation | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Gastritis | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Gastrointestinal haemorrhage | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Haematochezia | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Haemoperitoneum | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Ileus | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Large intestine polyp | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Mechanical ileus | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Oesophageal motility disorder | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Pancreatitis | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Rectal haemorrhage | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Vomiting | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
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| Asthenia | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Chest pain | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Chills | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Condition aggravated | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Death | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Disease progression | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 23.1 | Systematic Assessment |
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| General physical health deterioration | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Generalised oedema | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Inflammation | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Influenza like illness | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Multiple organ dysfunction syndrome | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Pain | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Performance status decreased | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Pyrexia | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Sudden death | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Swelling | General disorders | MedDRA 23.1 | Systematic Assessment |
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| Autoimmune hepatitis | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
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| Cholecystitis | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
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| Cholecystitis acute | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
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| Cholelithiasis | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
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| Hepatic failure | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
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| Hepatitis | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
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| Jaundice | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
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| Anaphylactic shock | Immune system disorders | MedDRA 23.1 | Systematic Assessment |
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| Cytokine release syndrome | Immune system disorders | MedDRA 23.1 | Systematic Assessment |
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| Abscess | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Anal abscess | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Appendicitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Atypical pneumonia | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Bronchitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Bronchopulmonary aspergillosis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Cellulitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Chorioretinitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Dermo-hypodermitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Diverticulitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Encephalitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Erysipelas | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Escherichia sepsis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Extradural abscess | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Gastroenteritis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Herpes zoster | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Infected cyst | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Influenza | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Localised infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Lower respiratory tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Lymph gland infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Meningitis aseptic | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Nasopharyngitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Periorbital cellulitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Postoperative wound infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Pulmonary sepsis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Pyelonephritis chronic | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Respiratory tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Scrotal abscess | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Sepsis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Sinusitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Tooth abscess | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Tracheobronchitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Upper respiratory tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Ureteritis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Urinary tract infection bacterial | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Urosepsis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
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| Wound infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Bone contusion | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Femur fracture | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Humerus fracture | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Multiple fractures | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Overdose | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Pseudomeningocele | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Radius fracture | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Skin laceration | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Spinal compression fracture | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Synovial rupture | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Toxicity to various agents | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Traumatic arthritis | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Upper limb fracture | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| General physical condition abnormal | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Diabetes mellitus | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Diabetic ketoacidosis | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Tumour lysis syndrome | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Type 1 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Type 2 diabetes mellitus | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Arthropathy | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Intervertebral disc degeneration | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Joint effusion | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Lumbar spinal stenosis | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Myositis | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pathological fracture | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Polyarthritis | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Psoriatic arthropathy | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Spinal pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Adenocarcinoma gastric | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Adenocarcinoma of colon | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Bladder adenocarcinoma stage unspecified | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Breast cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Endometrial cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Intraductal proliferative breast lesion | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Melanoma recurrent | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Metastases to bone | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Metastases to central nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Metastases to lung | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Metastases to nervous system | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Metastatic malignant melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Squamous cell carcinoma of skin | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Transitional cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Tumour associated fever | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Altered state of consciousness | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Basal ganglia infarction | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Carotid artery stenosis | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Central nervous system necrosis | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Cerebral haemorrhage | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dementia | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Embolic stroke | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Facial paralysis | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hydrocephalus | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Ischaemic cerebral infarction | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Ischaemic stroke | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Migraine | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Nervous system disorder | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Neurological symptom | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Paraparesis | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Paraplegia | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Speech disorder | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Spinal cord compression | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Completed suicide | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Mental status changes | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Obsessive-compulsive disorder | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Somatic symptom disorder | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Nephrotic syndrome | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Renal colic | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Renal impairment | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Ureteric obstruction | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Gynaecomastia | Reproductive system and breast disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Immune-mediated pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Interstitial lung disease | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Lung infiltration | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pneumothorax spontaneous | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pulmonary sarcoidosis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Sleep apnoea syndrome | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dermatitis | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dermatitis bullous | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Drug eruption | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Skin hypopigmentation | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Skin ulcer | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Stevens-Johnson syndrome | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Axillary lymphadenectomy | Surgical and medical procedures | MedDRA 23.1 | Systematic Assessment |
| |
| Arteritis | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Deep vein thrombosis | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Haemorrhage | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypertensive crisis | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Labile blood pressure | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Peripheral artery occlusion | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Subclavian vein thrombosis | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Thrombophlebitis | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Vena cava thrombosis | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hyperthyroidism | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Visual impairment | Eye disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Abdominal pain upper | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dry mouth | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Frequent bowel movements | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Face oedema | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Injection site reaction | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Oral herpes | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Contusion | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Aspartate aminotransferase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Blood alkaline phosphatase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Blood iron decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Neuropathy peripheral | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Actinic keratosis | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Rash erythematous | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Rash macular | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Skin mass | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Urticaria | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Vitiligo | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
|
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Study Director | Amgen Inc. | 866-572-6436 | medinfo@amgen.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jan 16, 2020 | Mar 8, 2022 | SAP_001.pdf |
| ID | Term |
|---|---|
| D008545 | Melanoma |
| ID | Term |
|---|---|
| D018358 | Neuroendocrine Tumors |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D009380 | Neoplasms, Nerve Tissue |
| D018326 | Nevi and Melanomas |
| D012878 | Skin Neoplasms |
| D009371 | Neoplasms by Site |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000629782 | talimogene laherparepvec |
| C582435 | pembrolizumab |
Not provided
Not provided
Not provided
|
|
|
|
|
|
|
|
| OG001 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
|
|
|
| Phase 3: Talimogene Laherparepvec + Pembrolizumab |
Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
|
|
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|
|
|
|
|
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
| OG001 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
|
|
|
| OG001 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
|
|
|
| OG001 |
| Phase 3: Talimogene Laherparepvec + Pembrolizumab |
Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
|
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| OG001 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
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| OG001 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
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| OG001 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
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| OG001 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
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| OG001 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
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| OG001 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
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| OG001 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
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| OG001 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
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| OG001 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
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| OG001 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
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| OG001 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
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Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ plaque-forming units (PFU)/mL by intralesional injection on day 1 of week 1. Subsequent doses of talimogene laherparepvec at up to 4 mL of 10⁸ PFU/mL began 3 weeks after the first dose and were administered every 2 weeks until disappearance of injectable lesions, complete response (CR), confirmed disease progression (PD) per modified Immune-related Response Criteria (irRC), intolerance of study treatment, 24 months from the date of the first dose of pembrolizumab, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 2 weeks starting at the time of the third dose of talimogene laherparepvec (week 6) until confirmed PD per modified irRC, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
| OG001 | Phase 3: Placebo + Pembrolizumab | Participants received up to 4 mL placebo to talimogene laherparepvec by intralesional injection on day 1 of week 0. Subsequent doses of placebo (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, complete response per modified Immune-related Response Criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST) (iCR), confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of placebo, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
| OG002 | Phase 3: Talimogene Laherparepvec + Pembrolizumab | Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first. |
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