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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-000307-32 | EudraCT Number |
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Phase 1b of the study will evaluate the safety of talimogene laherparepvec in combination with ipilimumab. Phase 2 is a randomized study that will evaluate the safety and efficacy of talimogene laherparepvec in combination with ipilimumab versus ipilumumab alone.
The phase 1b part is an open-label, multicenter, single-arm study where all participants will receive talimogene laherparepvec in combination with ipilimumab.
The phase 2 part of the study is an open-label, multicenter, randomized study to further assess the safety and to evaluate the efficacy of talimogene laherparepvec in combination with ipilimumab. Participants will be randomized 1:1 to receive talimogene laherparepvec plus ipilimumab or ipilimumab alone.
Participants randomized before amendment 2 will be stratified by stage of disease (stage IIIB/C, IVM1a, and stage IVM1b vs IVM1c) and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) V600E (a mutation resulting in a substitution of glutamic acid for valine at codon 600) (mutation vs mutation not present). Participants randomized after amendment 2 will be stratified by stage of disease (stage IIIB/C and IVM1a vs stage IVM1b and IVM1c) and prior therapy (treatment naïve vs previously treated with systemic anticancer immunotherapy vs previously treated with systemic anticancer treatment other than immunotherapy).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Phase 1b: Talimogene Laherparepvec + Ipilimumab | Experimental | Participants received talimogene laherparepvec at an initial dose of 10⁶ plaque-forming units (PFU)/mL injected into 1 or more skin, nodal, or subcutaneous tumors. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL began 3 weeks after the first dose and were administered every 2 weeks until complete response (CR), all injectable tumors had disappeared, confirmed disease progression per the modified immune-related response criteria (irRC), or intolerance of study treatment, whichever occurred first. Participants also received 3 mg/kg ipilimumab administered intravenously every 3 weeks for a total of 4 infusions starting at the time of the third dose of talimogene laherparepvec (week 6). |
|
| Phase 2: Ipilimumab | Active Comparator | Participants received ipilimumab 3 mg/kg intravenously every 3 weeks for a total of 4 infusions starting at week 1. |
|
| Phase 2: Talimogene Laherparepvec + Ipilimumab | Experimental | Participants received talimogene laherparepvec at an initial dose of 10⁶ PFU/mL injected into 1 or more skin, nodal, or subcutaneous tumors. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL began 3 weeks after the first dose and were administered every 2 weeks until CR, all injectable tumors had disappeared, confirmed disease progression per the modified irRC, or intolerance of study treatment, whichever occurred first. Participants also received 3 mg/kg ipilimumab intravenously every 3 weeks for a total of 4 infusions starting at the time of the third dose of talimogene laherparepvec (week 6). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Talimogene laherparepvec | Drug | Talimogene laherparepvec administered by intratumoral injection on Day 1 of Week 1, Day 1 of Week 4, then every two weeks thereafter. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1b: Number of Participants With Dose-limiting Toxicities | 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 version 3.0:
| The DLT evaluation period was 6 weeks from the initial administration of ipilimumab (week 6 to 12). |
| Phase 2: Objective Response Rate | Objective response rate is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) according to the modified immune-related response criteria (irRC) assessed by the investigator. Tumors were examined clinically and by computed tomography (CT) or magnetic resonance imaging (MRI). CR: Complete disappearance of all lesions and no new lesions; Any pathological lymph nodes reduced in short axis to <10 mm. PR: Decrease in tumor burden ≥ 50% relative to baseline. Response must have been confirmed by a repeat, consecutive assessment ≥ 4 weeks from the date first documented. Participants who did not have any follow-up tumor assessments were regarded as non-responders. | Tumor response was assessed every 12 weeks until disease progression; median follow-up time at the primary analysis was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
| Measure | Description | Time Frame |
|---|---|---|
| Phase 1b: Objective Response Rate | Objective response rate is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) according to the modified immune-related response criteria (irRC) assessed by the investigator. Tumors were examined clinically and by computed tomography (CT) or magnetic resonance imaging (MRI). CR: Complete disappearance of all lesions and no new lesions; Any pathological lymph nodes reduced in short axis to <10 mm. PR: Decrease in tumor burden ≥ 50% relative to baseline. Response must have been confirmed by a repeat, consecutive assessment ≥ 4 weeks from the date first documented. Participants who did not have any follow-up tumor assessments were regarded as non-responders. |
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Inclusion Criteria:
Histologically confirmed diagnosis of malignant melanoma.
Stage IIIB, IIIC, IVM1a, IVM1b, or IVM1c disease that is not suitable for surgical resection
Phase1: Treatment naïve: Must not have received any prior systemic anticancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy for unresected stage IIIB to IV melanoma.
Phase 2:
Measurable disease defined as one or both of the following
Injectable disease (ie, suitable for direct injection or through the use of ultrasound [US] guidance) defined as follows:
Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
Adequate hematologic, hepatic, renal, and coagulation functions
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Tucson | Arizona | 85724 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 28981385 | Background | Chesney J, Puzanov I, Collichio F, Singh P, Milhem MM, Glaspy J, Hamid O, Ross M, Friedlander P, Garbe C, Logan TF, Hauschild A, Lebbe C, Chen L, Kim JJ, Gansert J, Andtbacka RHI, Kaufman HL. Randomized, Open-Label Phase II Study Evaluating the Efficacy and Safety of Talimogene Laherparepvec in Combination With Ipilimumab Versus Ipilimumab Alone in Patients With Advanced, Unresectable Melanoma. J Clin Oncol. 2018 Jun 10;36(17):1658-1667. doi: 10.1200/JCO.2017.73.7379. Epub 2017 Oct 5. | |
| 27298410 |
| 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 1b all participants received talimogene laherparepvec in combination with ipilimumab. In Phase 2 participants were randomized in 1:1 ratio to receive talimogene laherparepvec plus ipilimumab or ipilimumab. Participants randomized prior to Protocol Amendment 2 were stratified by disease stage and v-raf murine sarcoma viral oncogene homolog B1 (BRAF) mutation V600E; participants randomized after Amendment 2 were stratified by disease stage and prior therapy.
This study was conducted at 33 centers in the United States of America, France, and Germany.
Participants were enrolled in Phase 1b from 07 February 2013 to 08 July 2013 and in Phase 2 from 13 August 2013 to 25 February 2016.
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| ID | Title | Description |
|---|---|---|
| FG000 | Phase 1b: Talimogene Laherparepvec + Ipilimumab | Participants received talimogene laherparepvec at an initial dose of 10⁶ plaque-forming units (PFU)/mL injected into 1 or more skin, nodal, or subcutaneous tumors with maximum total volume of 4 mL. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL total) began 3 weeks after the first dose and were administered every 2 weeks until complete response (CR), all injectable tumors had disappeared, confirmed disease progression per the modified immune-related response criteria (irRC), or intolerance of study treatment, whichever occurred first. Participants also received 3 mg/kg ipilimumab administered intravenously every 3 weeks for a total of 4 infusions starting at the time of the third dose of talimogene laherparepvec (week 6). |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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Phase 1b was an open-label, multicenter single-arm part of the study to evaluate safety of talimogene laherparepvec in combination with ipilimumab.
Phase 2 was an open-label multicenter, randomized design to further assess safety and to evaluate efficacy of talimogene laherparepvec in combination with ipilimumab.
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|
| Ipilimumab | Drug | Ipilimumab administered intravenously every 3 weeks for a total of 4 infusions. |
|
|
| Tumor response was assesed every 12 weeks until disease progression; median follow-up time at the primary analysis was 148.4 weeks. |
| Phase 2: Best Overall Response | Best overall response was categorized in descending order as a complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) or unevaluable (UE) based on investigator assessment according to the modified irRC. CR: Complete disappearance of all lesions and no new lesions; Any pathological lymph nodes reduced in short axis to <10 mm. PR: Decrease in tumor burden ≥ 50% relative to baseline. PD: Increase in tumor burden ≥ 25% relative to nadir. SD: Not meeting criteria for CR or PR, in absence of PD and no earlier than 77 days after the date of enrollment/randomization. CR, PR and PD must have been confirmed at 2 consecutive assessment ≥ 4 weeks apart. Assessments occurring after the start of the first subsequent anticancer therapy or removal of a lesion were not included. | Tumor response was assessed every 12 weeks until disease progression; median follow-up time at the primary analysis was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
| Phase 2: Disease Control Rate | Disease control rate (DCR) was defined as the percentage of participants with a best overall response of CR, PR or SD based on investigator assessment according to the modified irRC. CR: Complete disappearance of all lesions and no new lesions; any pathological lymph nodes reduced in short axis to <10 mm. PR: Decrease in tumor burden ≥ 50% relative to baseline. SD: Not meeting criteria for CR or PR, in absence of PD and no earlier than 77 days after the date of enrollment/randomization. CR and PR must have been confirmed at 2 consecutive assessments ≥ 4 weeks apart. | Tumor response was assessed every 12 weeks until disease progression; median follow-up time at the primary analysis was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
| Phase 2: Durable Response Rate | Durable response rate (DRR) was defined as the percentage of participants with a duration of response (best response of CR or PR) per modified irRC of at least 6 months. Duration of response is the time from the first confirmed CR or PR to confirmed disease progression per the modified irRC or death, whichever occurs earlier. | Tumor response was assessed every 12 weeks until disease progression; median follow-up time at the primary analysis was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
| Phase 2: Time to Response | Time to confirmed response (TTR) was defined as the time from randomization to the date of the first confirmed CR or PR per modified irRC criteria. Participants who did not have a confirmed CR or PR were censored at their last evaluable tumor assessment date. | Tumor response was assessed every 12 weeks until disease progression; median follow-up time at the primary analysis was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
| Phase 2: Duration of Response | Duration of response was calculated only for participants with an objective response per modified irRC and was defined as the time from first confirmed objective response (CR or PR) to confirmed disease progression per the modified irRC or death, whichever was earlier. Responders who did not have an event of death or disease progression were censored at their last evaluable tumor assessment date. | Tumor response was assessed every 12 weeks until disease progression; median follow-up time at the primary analysis was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
| Phase 2: Progression-free Survival | Progression-free survival was measured from the date of randomization to the date of disease progression (as measured by modified irRC) or death on or before the data cutoff date, whichever occurred first. Participants who had no disease progression and did not die while on study were censored at the last disease assessment date. | From randomization until the primary analysis data cut-off date of 23 August 2016; median follow-up time was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
| Phase 2: Resection Rate | Resection rate was defined as the percentage of participants who had surgical procedures for melanoma that resulted in a partial reduction or complete eradication of all previously unresectable cutaneous or visceral metastatic disease. Surgical procedures for melanoma with palliative intent (eg, for pain control) in the presence of disease progression were not considered resection. | From randomization until the primary analysis data cut-off date of 23 August 2016; median follow-up time was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
| Phase 2: Overall Survival | Overall survival was defined as the time from the date of randomization to the date of death from any cause. Participants without an event were censored at the last date they were known to be alive. Participants with a vital status obtained after the data cut-off were censored at the date cut-off date. | From randomization until the primary analysis data cut-off date of 23 August 2016; median follow-up time was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
| Phase 2: Kaplan-Meier Estimate of Percentage of Participants Alive at Month 12 and 24 | The overall survival estimates at month 24 data were not mature as most participants had not been followed for 24 months at the time of data cutoff. | Months 12 and 24; The median (Q1, Q3) follow-up time from randomization to the primary analysis data cutoff date was 80.6 (58.3, 106.3) weeks. |
| Phase 2: Progression-free Survival - Final Analysis | Progression-free survival was measured from the date of randomization to the date of disease progression (as measured by modified irRC) or death, whichever occurred first. Participants who had no disease progression and did not die while on study were censored at the last disease assessment date. | From randomization until the end of study (09 March 2021); median follow-up time was 155 weeks in the Ipilimumab group and 214 weeks in the Talimogene Laherparepvec + Ipilimumab group. |
| Phase 2: Overall Survival - Final Analysis | Overall survival was defined as the time from the date of randomization to the date of death from any cause. Participants without an event were censored at the last date they were known to be alive. | From randomization until the end of study (09 March 2021); median follow-up time was 155 weeks in the Ipilimumab group and 214 weeks in the Talimogene Laherparepvec + Ipilimumab group. |
| Phase 2: Kaplan-Meier Estimate of Percentage of Participants Alive at Month 12 and 24 - Final Analysis | Months 12 and 24 |
| Number of Participants With Adverse Events | Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, where grade 1 = mild AE, grade 2 = moderate AE, grade 3 = severe AE, grade 4 = life-threatening or disabling AE and grade 5 = death related to AE. The investigator assessed whether each AE was possibly related to talimogene laherparepvec (T-VEC) and/or ipilimumab (Ipi). | From first dose of study drug to 30 days after last dose of T-VEC or 60 days after last dose of Ipi, whichever was later; median duration of treatment was 14.7 weeks in Phase 1b T-VEC + Ipi, 9.1 weeks in Phase 2 Ipi, and 21.1 weeks in Phase 2 T-VEC + Ipi. |
| Beverly Hills |
| California |
| 90211 |
| United States |
| Research Site | Los Angeles | California | 90025 | United States |
| Research Site | Los Angeles | California | 90089-2211 | United States |
| Research Site | Los Angeles | California | 90095 | United States |
| Research Site | San Francisco | California | 94115 | United States |
| Research Site | Santa Rosa | California | 95403 | United States |
| Research Site | Aurora | Colorado | 80045 | United States |
| Research Site | Jacksonville | Florida | 32207 | United States |
| Research Site | Jacksonville | Florida | 32224 | United States |
| Research Site | Lakeland | Florida | 33805 | United States |
| Research Site | Miami | Florida | 33140 | United States |
| Research Site | Chicago | Illinois | 60612 | United States |
| Research Site | Indianapolis | Indiana | 46202 | United States |
| Research Site | Indianapolis | Indiana | 46260 | United States |
| Research Site | Iowa City | Iowa | 52242 | United States |
| Research Site | Louisville | Kentucky | 40202 | United States |
| Research Site | Minneapolis | Minnesota | 55407 | United States |
| Research Site | St Louis | Missouri | 63110 | United States |
| Research Site | Morristown | New Jersey | 07962 | United States |
| Research Site | New Brunswick | New Jersey | 08903 | United States |
| Research Site | New York | New York | 10029 | United States |
| Research Site | New York | New York | 10032 | United States |
| Research Site | Chapel Hill | North Carolina | 27599 | United States |
| Research Site | Canton | Ohio | 44718 | United States |
| Research Site | Cincinnati | Ohio | 45267 | United States |
| Research Site | Charleston | South Carolina | 29425 | United States |
| Research Site | Nashville | Tennessee | 37232 | United States |
| Research Site | Houston | Texas | 77030 | United States |
| Research Site | Salt Lake City | Utah | 84112 | United States |
| Research Site | Richmond | Virginia | 23298-0037 | United States |
| Research Site | Milwaukee | Wisconsin | 53226 | United States |
| Research Site | Bordeaux | 33075 | France |
| Research Site | Grenoble | 38043 | France |
| Research Site | Lille | 59037 | France |
| Research Site | Nantes | 44093 | France |
| Research Site | Paris | 75010 | France |
| Research Site | Göttingen | 37075 | Germany |
| Research Site | Kiel | 24105 | Germany |
| Research Site | Tübingen | 72076 | Germany |
| Background |
| Puzanov I, Milhem MM, Minor D, Hamid O, Li A, Chen L, Chastain M, Gorski KS, Anderson A, Chou J, Kaufman HL, Andtbacka RH. Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma. J Clin Oncol. 2016 Aug 1;34(22):2619-26. doi: 10.1200/JCO.2016.67.1529. Epub 2016 Jun 13. |
| 31353364 | Background | Chesney J, Puzanov I, Collichio F, Milhem MM, Hauschild A, Chen L, Sharma A, Garbe C, Singh P, Mehnert JM. Patterns of response with talimogene laherparepvec in combination with ipilimumab or ipilimumab alone in metastatic unresectable melanoma. Br J Cancer. 2019 Aug;121(5):417-420. doi: 10.1038/s41416-019-0530-6. Epub 2019 Jul 29. |
| 28238174 | 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. |
| 37142291 | Background | Chesney JA, Puzanov I, Collichio FA, Singh P, Milhem MM, Glaspy J, Hamid O, Ross M, Friedlander P, Garbe C, Logan T, Hauschild A, Lebbe C, Joshi H, Snyder W, Mehnert JM. Talimogene laherparepvec in combination with ipilimumab versus ipilimumab alone for advanced melanoma: 5-year final analysis of a multicenter, randomized, open-label, phase II trial. J Immunother Cancer. 2023 May;11(5):e006270. doi: 10.1136/jitc-2022-006270. |
| FG001 | Phase 2: Ipilimumab | Participants received ipilimumab 3 mg/kg intravenously every 3 weeks for a total of 4 infusions starting at week 1. |
| FG002 | Phase 2: Talimogene Laherparepvec + Ipilimumab | Participants received talimogene laherparepvec at an initial dose of 10⁶ PFU/mL injected into 1 or more skin, nodal, or subcutaneous tumors with a maximum total volume of 4 mL. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL total) began 3 weeks after the first dose and were administered every 2 weeks until CR, all injectable tumors had disappeared, confirmed disease progression per the modified irRC, or intolerance of study treatment, whichever occurred first. Participants also received 3 mg/kg ipilimumab intravenously every 3 weeks for a total of 4 infusions starting at the time of the third dose of talimogene laherparepvec (week 6). |
| Received Talimogene Laherparepvec |
|
| Received Ipilimumab |
|
| COMPLETED | Completed study |
|
| NOT COMPLETED |
|
|
All enrolled participants
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| ID | Title | Description |
|---|---|---|
| BG000 | Phase 1b: Talimogene Laherparepvec + Ipilimumab | Participants received talimogene laherparepvec at an initial dose of 10⁶ plaque-forming units (PFU)/mL injected into 1 or more skin, nodal, or subcutaneous tumors with maximum total volume of 4 mL. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL total) began 3 weeks after the first dose and were administered every 2 weeks until complete response (CR), all injectable tumors had disappeared, confirmed disease progression per the modified immune-related response criteria (irRC), or intolerance of study treatment, whichever occurred first. Participants also received 3 mg/kg ipilimumab administered intravenously every 3 weeks for a total of 4 infusions starting at the time of the third dose of talimogene laherparepvec (week 6). |
| BG001 | Phase 2: Ipilimumab | Participants received ipilimumab 3 mg/kg intravenously every 3 weeks for a total of 4 infusions starting at week 1. |
| BG002 | Phase 2: Talimogene Laherparepvec + Ipilimumab | Participants received talimogene laherparepvec at an initial dose of 10⁶ PFU/mL injected into 1 or more skin, nodal, or subcutaneous tumors with a maximum total volume of 4 mL. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL total) began 3 weeks after the first dose and were administered every 2 weeks until CR, all injectable tumors had disappeared, confirmed disease progression per the modified irRC, or intolerance of study treatment, whichever occurred first. Participants also received 3 mg/kg ipilimumab intravenously every 3 weeks for a total of 4 infusions starting at the time of the third dose of talimogene laherparepvec (week 6). |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
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| Age, Customized | Count of Participants | Participants |
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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 |
| ||||||||||||||||
| Eastern Cooperative Oncology Group (ECOG) Performance Status | Scale used to assess how a patient's disease is progressing, how the disease affects the daily living abilities of the patient: 0 = Fully active, able to carry on all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory, able to carry out work of a light nature; 2 = Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about > 50% of waking hours; 3 = Capable of only limited self care, confined to a bed or chair > 50% of waking hours; 4 = Completely disabled, confined to bed or chair; 5 = Dead. | Count of Participants | Participants |
| |||||||||||||||
| Tumor, Node, Metastasis (TNM) Disease Stage | 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 |
| |||||||||||||||
| 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 |
|
| 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 | ||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Phase 1b: Number of Participants With Dose-limiting Toxicities | 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 version 3.0:
| All phase 1b participants who received ≥ 1 dose of investigational product (talimogene laherparepvec or ipilimumab). | Posted | Count of Participants | Participants | The DLT evaluation period was 6 weeks from the initial administration of ipilimumab (week 6 to 12). |
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| Primary | Phase 2: Objective Response Rate | Objective response rate is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) according to the modified immune-related response criteria (irRC) assessed by the investigator. Tumors were examined clinically and by computed tomography (CT) or magnetic resonance imaging (MRI). CR: Complete disappearance of all lesions and no new lesions; Any pathological lymph nodes reduced in short axis to <10 mm. PR: Decrease in tumor burden ≥ 50% relative to baseline. Response must have been confirmed by a repeat, consecutive assessment ≥ 4 weeks from the date first documented. Participants who did not have any follow-up tumor assessments were regarded as non-responders. | All participants randomized in phase 2 | Posted | Number | 95% Confidence Interval | percentage of participants | Tumor response was assessed every 12 weeks until disease progression; median follow-up time at the primary analysis was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
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| Secondary | Phase 1b: Objective Response Rate | Objective response rate is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) according to the modified immune-related response criteria (irRC) assessed by the investigator. Tumors were examined clinically and by computed tomography (CT) or magnetic resonance imaging (MRI). CR: Complete disappearance of all lesions and no new lesions; Any pathological lymph nodes reduced in short axis to <10 mm. PR: Decrease in tumor burden ≥ 50% relative to baseline. Response must have been confirmed by a repeat, consecutive assessment ≥ 4 weeks from the date first documented. Participants who did not have any follow-up tumor assessments were regarded as non-responders. | All phase 1b participants who received ≥ 1 dose of investigational product (talimogene laherparepvec or ipilimumab). | Posted | Number | 95% Confidence Interval | percentage of participants | Tumor response was assesed every 12 weeks until disease progression; median follow-up time at the primary analysis was 148.4 weeks. |
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| Secondary | Phase 2: Best Overall Response | Best overall response was categorized in descending order as a complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD) or unevaluable (UE) based on investigator assessment according to the modified irRC. CR: Complete disappearance of all lesions and no new lesions; Any pathological lymph nodes reduced in short axis to <10 mm. PR: Decrease in tumor burden ≥ 50% relative to baseline. PD: Increase in tumor burden ≥ 25% relative to nadir. SD: Not meeting criteria for CR or PR, in absence of PD and no earlier than 77 days after the date of enrollment/randomization. CR, PR and PD must have been confirmed at 2 consecutive assessment ≥ 4 weeks apart. Assessments occurring after the start of the first subsequent anticancer therapy or removal of a lesion were not included. | All participants randomized in phase 2 | Posted | Count of Participants | Participants | Tumor response was assessed every 12 weeks until disease progression; median follow-up time at the primary analysis was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
| ||||||||||||||||||||||||||||
| Secondary | Phase 2: Disease Control Rate | Disease control rate (DCR) was defined as the percentage of participants with a best overall response of CR, PR or SD based on investigator assessment according to the modified irRC. CR: Complete disappearance of all lesions and no new lesions; any pathological lymph nodes reduced in short axis to <10 mm. PR: Decrease in tumor burden ≥ 50% relative to baseline. SD: Not meeting criteria for CR or PR, in absence of PD and no earlier than 77 days after the date of enrollment/randomization. CR and PR must have been confirmed at 2 consecutive assessments ≥ 4 weeks apart. | All participants randomized in phase 2 | Posted | Number | 95% Confidence Interval | percentage of participants | Tumor response was assessed every 12 weeks until disease progression; median follow-up time at the primary analysis was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
| |||||||||||||||||||||||||||
| Secondary | Phase 2: Durable Response Rate | Durable response rate (DRR) was defined as the percentage of participants with a duration of response (best response of CR or PR) per modified irRC of at least 6 months. Duration of response is the time from the first confirmed CR or PR to confirmed disease progression per the modified irRC or death, whichever occurs earlier. | All participants randomized in phase 2 | Posted | Number | 95% Confidence Interval | percentage of participants | Tumor response was assessed every 12 weeks until disease progression; median follow-up time at the primary analysis was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
| |||||||||||||||||||||||||||
| Secondary | Phase 2: Time to Response | Time to confirmed response (TTR) was defined as the time from randomization to the date of the first confirmed CR or PR per modified irRC criteria. Participants who did not have a confirmed CR or PR were censored at their last evaluable tumor assessment date. | All participants randomized in phase 2 | Posted | Median | 95% Confidence Interval | months | Tumor response was assessed every 12 weeks until disease progression; median follow-up time at the primary analysis was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
| |||||||||||||||||||||||||||
| Secondary | Phase 2: Duration of Response | Duration of response was calculated only for participants with an objective response per modified irRC and was defined as the time from first confirmed objective response (CR or PR) to confirmed disease progression per the modified irRC or death, whichever was earlier. Responders who did not have an event of death or disease progression were censored at their last evaluable tumor assessment date. | Participants randomized in phase 2 with a confirmed CR or PR. | Posted | Median | 95% Confidence Interval | months | Tumor response was assessed every 12 weeks until disease progression; median follow-up time at the primary analysis was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
| |||||||||||||||||||||||||||
| Secondary | Phase 2: Progression-free Survival | Progression-free survival was measured from the date of randomization to the date of disease progression (as measured by modified irRC) or death on or before the data cutoff date, whichever occurred first. Participants who had no disease progression and did not die while on study were censored at the last disease assessment date. | All participants randomized in phase 2 | Posted | Median | 95% Confidence Interval | months | From randomization until the primary analysis data cut-off date of 23 August 2016; median follow-up time was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
| |||||||||||||||||||||||||||
| Secondary | Phase 2: Resection Rate | Resection rate was defined as the percentage of participants who had surgical procedures for melanoma that resulted in a partial reduction or complete eradication of all previously unresectable cutaneous or visceral metastatic disease. Surgical procedures for melanoma with palliative intent (eg, for pain control) in the presence of disease progression were not considered resection. | All participants randomized in phase 2 | Posted | Number | 95% Confidence Interval | percentage of participants | From randomization until the primary analysis data cut-off date of 23 August 2016; median follow-up time was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
| |||||||||||||||||||||||||||
| Secondary | Phase 2: Overall Survival | Overall survival was defined as the time from the date of randomization to the date of death from any cause. Participants without an event were censored at the last date they were known to be alive. Participants with a vital status obtained after the data cut-off were censored at the date cut-off date. | All participants randomized in phase 2 | Posted | Median | 95% Confidence Interval | months | From randomization until the primary analysis data cut-off date of 23 August 2016; median follow-up time was 57.7 weeks and 68.1 weeks in each treatment group respectively. |
| |||||||||||||||||||||||||||
| Secondary | Phase 2: Kaplan-Meier Estimate of Percentage of Participants Alive at Month 12 and 24 | The overall survival estimates at month 24 data were not mature as most participants had not been followed for 24 months at the time of data cutoff. | All participants randomized in phase 2 | Posted | Number | 95% Confidence Interval | percentage of participants | Months 12 and 24; The median (Q1, Q3) follow-up time from randomization to the primary analysis data cutoff date was 80.6 (58.3, 106.3) weeks. |
| |||||||||||||||||||||||||||
| Secondary | Phase 2: Progression-free Survival - Final Analysis | Progression-free survival was measured from the date of randomization to the date of disease progression (as measured by modified irRC) or death, whichever occurred first. Participants who had no disease progression and did not die while on study were censored at the last disease assessment date. | All participants randomized in phase 2 | Posted | Median | 95% Confidence Interval | months | From randomization until the end of study (09 March 2021); median follow-up time was 155 weeks in the Ipilimumab group and 214 weeks in the Talimogene Laherparepvec + Ipilimumab group. |
| |||||||||||||||||||||||||||
| Secondary | Phase 2: Overall Survival - Final Analysis | Overall survival was defined as the time from the date of randomization to the date of death from any cause. Participants without an event were censored at the last date they were known to be alive. | All participants randomized in phase 2 | Posted | Median | 95% Confidence Interval | months | From randomization until the end of study (09 March 2021); median follow-up time was 155 weeks in the Ipilimumab group and 214 weeks in the Talimogene Laherparepvec + Ipilimumab group. |
| |||||||||||||||||||||||||||
| Secondary | Phase 2: Kaplan-Meier Estimate of Percentage of Participants Alive at Month 12 and 24 - Final Analysis | All participants randomized in phase 2 | Posted | Number | 95% Confidence Interval | percentage of participants | Months 12 and 24 |
|
| |||||||||||||||||||||||||||
| Secondary | Number of Participants With Adverse Events | Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0, where grade 1 = mild AE, grade 2 = moderate AE, grade 3 = severe AE, grade 4 = life-threatening or disabling AE and grade 5 = death related to AE. The investigator assessed whether each AE was possibly related to talimogene laherparepvec (T-VEC) and/or ipilimumab (Ipi). | All participants who received ≥ 1 dose of investigational product (talimogene laherparepvec or ipilimumab). | Posted | Count of Participants | Participants | From first dose of study drug to 30 days after last dose of T-VEC or 60 days after last dose of Ipi, whichever was later; median duration of treatment was 14.7 weeks in Phase 1b T-VEC + Ipi, 9.1 weeks in Phase 2 Ipi, and 21.1 weeks in Phase 2 T-VEC + Ipi. |
|
All-cause mortality is reported from randomization until the end of study (09 March 2021); median follow-up time was 271 weeks in Phase 1, 155 weeks in the Phase 2 Ipilimumab group and 214 weeks in the Phase 2 T-VEC + Ipilimumab group. AEs are reported from first dose of study drug until 30 days after last dose of talimogene laherparepvec or 60 days after last dose of ipilimumab, whichever was later; median duration of treatment was 14.7, 9.1, and 21.1 weeks in each treatment group respectively.
All-cause mortality is reported for all enrolled (Phase 1b) or randomized (Phase 2) participants.
Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug (talimogene laherparepvec or ipilimumab).
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 + Ipilimumab | Participants received talimogene laherparepvec at an initial dose of 10⁶ plaque-forming units (PFU)/mL injected into 1 or more skin, nodal, or subcutaneous tumors with maximum total volume of 4 mL. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL total) began 3 weeks after the first dose and were administered every 2 weeks until complete response (CR), all injectable tumors had disappeared, confirmed disease progression per the modified immune-related response criteria (irRC), or intolerance of study treatment, whichever occurred first. Participants also received 3 mg/kg ipilimumab administered intravenously every 3 weeks for a total of 4 infusions starting at the time of the third dose of talimogene laherparepvec (week 6). | 9 | 19 | 6 | 19 | 19 | 19 |
| EG001 | Phase 2: Ipilimumab | Participants received ipilimumab 3 mg/kg intravenously every 3 weeks for a total of 4 infusions starting at week 1. | 52 | 100 | 34 | 95 | 85 | 95 |
| EG002 | Phase 2: Talimogene Laherparepvec + Ipilimumab | Participants received talimogene laherparepvec at an initial dose of 10⁶ PFU/mL injected into 1 or more skin, nodal, or subcutaneous tumors with a maximum total volume of 4 mL. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL total) began 3 weeks after the first dose and were administered every 2 weeks until CR, all injectable tumors had disappeared, confirmed disease progression per the modified irRC, or intolerance of study treatment, whichever occurred first. Participants also received 3 mg/kg ipilimumab intravenously every 3 weeks for a total of 4 infusions starting at the time of the third dose of talimogene laherparepvec (week 6). | 45 | 98 | 34 | 95 | 91 | 95 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Angina pectoris | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Arrhythmia | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypophysitis | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Lymphocytic hypophysitis | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Exophthalmos | Eye disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Abdominal distension | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Autoimmune colitis | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Injection site reaction | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Autoimmune hepatitis | Hepatobiliary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Cytomegalovirus colitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Meningitis aseptic | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Hip fracture | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Amylase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Blood creatinine increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Neutrophil count decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| White blood cell count decreased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hyponatraemia | 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 |
| |
| Lumbar spinal stenosis | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | 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 |
| |
| Malignant pleural effusion | 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 |
| |
| Tumour flare | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Facial paralysis | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Intracranial mass | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Seizure | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Haematuria | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Rash maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Adrenocortical insufficiency acute | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Anal fissure | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Osteomyelitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Lumbar vertebral fracture | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Myositis | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Encephalopathy | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Drug reaction with eosinophilia and systemic symptoms | Skin and subcutaneous tissue 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 |
| |
| Lymphopenia | Blood and lymphatic system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Adrenal insufficiency | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Lymphocytic hypophysitis | Endocrine disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Eye pain | Eye disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Uveitis | Eye disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Vision blurred | Eye disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Application site pain | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Chills | 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 inflammation | 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 |
| |
| Injection site swelling | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Malaise | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Oedema peripheral | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Performance status decreased | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Peripheral swelling | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Escherichia infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Eye infection | 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 |
| |
| Sinusitis | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Vaginal infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Vulvovaginal mycotic infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA 23.1 | Systematic Assessment |
| |
| Radius fracture | Injury, poisoning and procedural complications | MedDRA 23.1 | Systematic Assessment |
| |
| Alanine aminotransferase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Amylase 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 lactate dehydrogenase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Lipase increased | Investigations | MedDRA 23.1 | Systematic Assessment |
| |
| Weight decreased | 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 |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypomagnesaemia | 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 |
| |
| Muscle tightness | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | 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 |
| |
| Pubic pain | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Soft tissue mass | Musculoskeletal and connective tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.1 | Systematic Assessment |
| |
| Brain oedema | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Cluster headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Peripheral motor neuropathy | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Peripheral sensory neuropathy | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Speech disorder | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Tension headache | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Tremor | Nervous system disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Nightmare | Psychiatric disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Bladder pain | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dysuria | Renal and urinary disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pollakiuria | Renal and urinary 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 |
| |
| Hiccups | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Dry skin | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Erythema | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Night sweats | 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 maculo-papular | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Skin disorder | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Skin lesion | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Vitiligo | Skin and subcutaneous tissue disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Embolism | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hot flush | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Haematochezia | Gastrointestinal disorders | MedDRA 23.1 | Systematic Assessment |
| |
| Hyponatraemia | Metabolism and nutrition 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 |
| 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 |
| D000074324 | Ipilimumab |
| ID | Term |
|---|---|
| D061067 | Antibodies, Monoclonal, Humanized |
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
| D001798 | Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |
Not provided
Not provided
| ≥ 65 years |
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| Male |
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| Not Hispanic or Latino |
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| Unknown or Not Reported |
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| Asian |
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| Black (or African American) |
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| Multiple |
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| Native Hawaiian or Other Pacific Islander |
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| White |
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| Other |
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| 1 (Restrictive but ambulatory) |
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| Stage IVM1b/c |
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| Wild-type |
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| Missing/Unknown |
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| Units | Counts |
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| Participants |
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| OG001 | Phase 2: Ipilimumab | Participants received ipilimumab 3 mg/kg intravenously every 3 weeks for a total of 4 infusions starting at week 1. |
| OG002 | Phase 2: Talimogene Laherparepvec + Ipilimumab | Participants received talimogene laherparepvec at an initial dose of 10⁶ PFU/mL injected into 1 or more skin, nodal, or subcutaneous tumors with a maximum total volume of 4 mL. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL total) began 3 weeks after the first dose and were administered every 2 weeks until CR, all injectable tumors had disappeared, confirmed disease progression per the modified irRC, or intolerance of study treatment, whichever occurred first. Participants also received 3 mg/kg ipilimumab intravenously every 3 weeks for a total of 4 infusions starting at the time of the third dose of talimogene laherparepvec (week 6). |
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