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| ID | Type | Description | Link |
|---|---|---|---|
| 20130232 / KEYNOTE-137 | Other Identifier | Merck / Amgen | |
| 2015-003011-38 | EudraCT Number |
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| Name | Class |
|---|---|
| Merck Sharp & Dohme LLC | INDUSTRY |
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The primary objective of this study was to evaluate the safety, as assessed by incidence of dose limiting toxicity (DLT), of talimogene laherparepvec in combination with pembrolizumab in adults with recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).
This is a phase 1b/3, multicenter, clinical trial conducted in 2 parts (phase 1b and phase 3). In phase 1b talimogene laherparepvec is to be administered in combination with pembrolizumab to adults with recurrent or metastatic squamous cell carcinoma of head and neck (SCCHN). Dose limiting toxicity (DLT) is to be evaluated based on the first 18 DLT-evaluable participants. An expansion cohort of up to an additional 22 treated patients could be enrolled to further evaluate the safety and to estimate the efficacy of the combination of talimogene laherparepvec with pembrolizumab and to support a decision to initiate the phase 3 part of the study. The phase 3 part of the study was designed as a multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy, as assessed by overall survival, of treatment with talimogene laherparepvec with pembrolizumab versus placebo with pembrolizumab in adults with recurrent or metastatic SCCHN, however, a decision was made not to proceed to the phase 3 part of the study.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Talimogene Laherparepvec + Pembrolizumab | Experimental | Talimogene laherparepvec is administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL 3 weeks after the initial dose and every 3 weeks (Q3W) thereafter. Pembrolizumab is administered by intravenous infusion at a dose of 200 mg Q3W after the initial dose. Participants are treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Talimogene Laherparepvec | Drug | The initial dose of talimogene laherparepvec is up to 8.0 mL of 10⁶ PFU/mL. Subsequent doses of talimogene laherparepvec are up to 8.0 mL of 10⁸ PFU/mL. |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With a Dose Limiting Toxicity (DLT) | The following toxicities (graded per the Common Terminology Criteria for Adverse Events v 4.0) were considered DLTs if judged by the investigator to be related to either study drug:
| First 6 weeks after the initial administration of talimogene laherparepvec and pembrolizumab in combination |
| Measure | Description | Time Frame |
|---|---|---|
| Objective Response Rate | Objective response rate was defined as the percentage of participants with a best overall response of complete response or partial response assessed by the investigator using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Response was based on the size of tumors assessed by computed tomography (CT) or magnetic resonance imaging (MRI). Complete response (iCR): Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (iPR): Decrease in tumor burden ≥ 30% relative to baseline. Confirmation by a consecutive assessment at least 4 weeks after first documentation required. Analyses are presented below for both the unconfirmed and confirmed results. |
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Inclusion Criteria
Male or female age ≥ 18 years at the time of informed consent
Histologically confirmed diagnosis of metastatic or recurrent SCCHN of the oral cavity, oropharynx, hypopharynx, or larynx. Disease must be unsuitable for curative surgical resection and must not be amenable to curative radiotherapy.
Disease must have progressed after treatment with a platinum-containing regimen and should be defined as one of the following:
i. disease progression or recurrence between 3 to 6 months of prior curatively intended multimodal therapy (which includes platinum therapy) for locoregionally advanced SCCHN.
ii. disease progression or recurrence after prior platinum therapy in the recurrent or metastatic setting Note: This criterion is only applicable for subjects who have not had treatment in the recurrent/metastatic setting
Subject must be candidate for intralesional therapy administration defined as one or more of the following:
i. at least 1 injectable cutaneous, subcutaneous, or nodal SCCHN tumor ≥ 10 mm in longest diameter ii. multiple injectable cutaneous, subcutaneous, or nodal SCCHN tumors that in aggregate have a longest diameter of ≥ 10 mm Note: Mucosal surfaces of tumor lesions and visceral metastases should not be injected.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
Adequate organ function determined within 14 days prior to enrollment
Female subject of childbearing potential must have a negative pregnancy test within 72 hours prior to enrollment.
Other Inclusion Criteria May Apply
Exclusion Criteria
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| Name | Affiliation | Role |
|---|---|---|
| MD | Amgen | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Site | Newark | Delaware | 19713 | United States | ||
| Research Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32669371 | Derived | Harrington KJ, Kong A, Mach N, Chesney JA, Fernandez BC, Rischin D, Cohen EEW, Radcliffe HS, Gumuscu B, Cheng J, Snyder W, Siu LL. Talimogene Laherparepvec and Pembrolizumab in Recurrent or Metastatic Squamous Cell Carcinoma of the Head and Neck (MASTERKEY-232): A Multicenter, Phase 1b Study. Clin Cancer Res. 2020 Oct 1;26(19):5153-5161. doi: 10.1158/1078-0432.CCR-20-1170. Epub 2020 Jul 15. |
| 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.
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This study was conducted at 19 centers in Australia, Canada, Europe, and the United States.
This study was designed to be conducted in 2 parts (phase 1b and phase 3). A decision was made not to initiate the phase 3 part of the study.
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| ID | Title | Description |
|---|---|---|
| FG000 | Talimogene Laherparepvec + Pembrolizumab | Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL every 3 weeks (Q3W) thereafter. Pembrolizumab was administered by intravenous infusion at a dose of 200 mg Q3W. Participants were treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, 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 | May 11, 2018 | Oct 19, 2018 |
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For Phase 1b there are no 'maskings' as it's open-label.
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| Pembrolizumab | Biological | Administered as a 30-minute intravenous infusion at a dose of 200 mg Q3W |
|
|
| Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks. |
| Complete Response Rate | Complete response rate (iCRR) was defined as the percentage of participants with a best overall response of complete response assessed by the investigator using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Response was based on the size of tumors assessed by computed tomography (CT) or magnetic resonance imaging (MRI). Complete response (iCR): Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Analyses are presented below for both the unconfirmed and confirmed results. | Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks. |
| Best Overall Confirmed Response | Best overall visit response of iCR, iPR, stable disease (iSD), progressive disease (iPD) or unevaluable (iUE) based on investigator assessment using irRECIST. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new). Any pathological lymph nodes (target or non-target) must have reduction in short axis to <10 mm. iPR: Decrease in tumor size ≥ 30% relative to baseline. iPD: Increase in tumor size ≥ 20% and at least 5 mm absolute increase compared to nadir or qualitative worsening of non-target lesions or a new lesion. iSD: Neither sufficient shrinkage to qualify for iCR or iPR nor sufficient increase to qualify for iPD. iUE: Any baseline lesion which was not assessed or was unable to be evaluated leading to an inability to determine the status of that particular tumor. Not Done: Radiographic imaging was not performed to evaluate the response. iCR, iPR, and iPD required confirmation by a consecutive assessment at least 4 weeks after first documentation. | Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks. |
| Duration of Confirmed Response | Duration of response (iDOR) per irRECIST was defined as the time from the date of an initial response of iCR or iPR that was subsequently confirmed to the earlier of a participant overall response of iPD or death. Participants who did not end their response at the time of analysis were censored at their last evaluable tumor assessment. | Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks. |
| Disease Control Rate | Disease control rate (iDCR) was defined as the percentage of participants with a best overall response of iCR or iPR or iSD assessed by the investigator using irRECIST. Complete response (iCR): Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (iPR): Decrease in tumor burden ≥ 30% relative to baseline. Confirmation by a consecutive assessment at least 4 weeks after first documentation required. Stable disease (iSD): Neither sufficient shrinkage to qualify for iCR or iPR nor sufficient increase to qualify for iPD. Analyses are presented below for both the unconfirmed and confirmed results. | Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks. |
| Progression Free Survival | Progression-free survival (iPFS) per irRECIST was defined as the interval from first dose to the earlier of a participant overall response of iPD or death from any cause; otherwise, iPFS was censored at the last evaluable tumor assessment. The initial date of an iPD that was consecutively confirmed was used. | Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks. |
| Overall Survival | Overall survival (OS) was defined as the interval from first dose to the event of death from any cause; otherwise, OS was censored at the date the participant was last known to be alive. | Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks. |
| Number of Participants With Adverse Events | The severity of adverse events was assessed by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, and based on the following scale: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death. A serious adverse event is an AE that met at least 1 of the following serious criteria:
| From first dose of study drug to 30 days after last dose; the median (range) duration of treatment was 5.6 (0.1 to 75.3) weeks for talimogene laherparepvec and 6.1 (0.1, 105.3) weeks for pembrolizumab. |
| Chicago |
| Illinois |
| 60611 |
| United States |
| Research Site | Chicago | Illinois | 60637 | United States |
| Research Site | Louisville | Kentucky | 40202 | United States |
| Research Site | Billings | Montana | 59101 | United States |
| Research Site | New York | New York | 10003 | United States |
| Research Site | New York | New York | 10021 | United States |
| Research Site | Canton | Ohio | 44718 | United States |
| Research Site | Geelong | Victoria | 3220 | Australia |
| Research Site | Melbourne | Victoria | 3000 | Australia |
| Research Site | Salzburg | 5020 | Austria |
| Research Site | Brussels | 1000 | Belgium |
| Research Site | Wilrijk | 2610 | Belgium |
| Research Site | Toronto | Ontario | M5G 2M9 | Canada |
| Research Site | Bordeaux | 33076 | France |
| Research Site | Pierre-Bénite | 69495 | France |
| Research Site | Toulouse | 31059 | France |
| Research Site | Athens | 12462 | Greece |
| Research Site | Ioannina | 45500 | Greece |
| Research Site | Milan | 20133 | Italy |
| Research Site | Seville | Andalusia | 41013 | Spain |
| Research Site | L'Hospitalet de Llobregat | Catalonia | 08907 | Spain |
| Research Site | Madrid | 28046 | Spain |
| Research Site | Madrid | 28050 | Spain |
| Research Site | Bellinzona | 6500 | Switzerland |
| Research Site | Geneva | 1211 | Switzerland |
| Research Site | Zurich | 8091 | Switzerland |
| Research Site | Birmingham | B15 2TT | United Kingdom |
| Research Site | London | SE1 7EH | United Kingdom |
| Research Site | London | SW3 6JJ | United Kingdom |
| Research Site | Metropolitan Borough of Wirral | CH63 4JY | United Kingdom |
| Research Site | Oxford | OX3 7LE | United Kingdom |
| Research Site | Sutton | SM2 5PT | United Kingdom |
| COMPLETED |
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| NOT COMPLETED |
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|
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| ID | Title | Description |
|---|---|---|
| BG000 | Talimogene Laherparepvec + Pembrolizumab | Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL every 3 weeks (Q3W) thereafter. Pembrolizumab was administered by intravenous infusion at a dose of 200 mg Q3W. Participants were treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. |
| 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 |
| |||||||||||||||||
| 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 |
| ||||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
| ||||||||||||||||||
| Eastern Cooperative Oncology Group (ECOG) Performance Status | A scale to assess a patient's disease status. 0 = Fully active, able to carry out all pre-disease performance without restriction; 1 = Restricted in physically strenuous activity, ambulatory and able to carry out work of a light nature; 2 = Ambulatory and capable of all self-care, unable to carry out any work activities. Up and about > 50% of waking hours; 3 = Capable of only limited self-care, confined to bed or chair > 50% of waking hours; 4 = Completely disabled, confined to bed or chair; 5 = Dead. | Count of Participants | Participants |
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| Herpes Simplex Virus Status | Count of Participants | Participants |
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| Primary Tumor Site | 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 | Number of Participants With a Dose Limiting Toxicity (DLT) | The following toxicities (graded per the Common Terminology Criteria for Adverse Events v 4.0) were considered DLTs if judged by the investigator to be related to either study drug:
| The DLT analysis set included DLT-evaluable participants who had the opportunity to be on treatment for at least 6 weeks and had received at least 2 doses of talimogene laherparepvec and 2 doses of pembrolizumab in combination, or who had a DLT during the DLT evaluation period after at least 1 dose of both study drugs in combination. | Posted | Count of Participants | Participants | First 6 weeks after the initial administration of talimogene laherparepvec and pembrolizumab in combination |
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| Secondary | Objective Response Rate | Objective response rate was defined as the percentage of participants with a best overall response of complete response or partial response assessed by the investigator using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Response was based on the size of tumors assessed by computed tomography (CT) or magnetic resonance imaging (MRI). Complete response (iCR): Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (iPR): Decrease in tumor burden ≥ 30% relative to baseline. Confirmation by a consecutive assessment at least 4 weeks after first documentation required. Analyses are presented below for both the unconfirmed and confirmed results. | The efficacy analysis set included all enrolled participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab, excluding participants with locoregionally advanced disease with a recurrence < 3 months after prior platinum-containing curatively intended multimodal therapy. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks. |
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| Secondary | Complete Response Rate | Complete response rate (iCRR) was defined as the percentage of participants with a best overall response of complete response assessed by the investigator using immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Response was based on the size of tumors assessed by computed tomography (CT) or magnetic resonance imaging (MRI). Complete response (iCR): Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Analyses are presented below for both the unconfirmed and confirmed results. | The efficacy analysis set included all enrolled participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab, excluding participants with locoregionally advanced disease with a recurrence < 3 months after prior platinum-containing curatively intended multimodal therapy. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks. |
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| Secondary | Best Overall Confirmed Response | Best overall visit response of iCR, iPR, stable disease (iSD), progressive disease (iPD) or unevaluable (iUE) based on investigator assessment using irRECIST. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new). Any pathological lymph nodes (target or non-target) must have reduction in short axis to <10 mm. iPR: Decrease in tumor size ≥ 30% relative to baseline. iPD: Increase in tumor size ≥ 20% and at least 5 mm absolute increase compared to nadir or qualitative worsening of non-target lesions or a new lesion. iSD: Neither sufficient shrinkage to qualify for iCR or iPR nor sufficient increase to qualify for iPD. iUE: Any baseline lesion which was not assessed or was unable to be evaluated leading to an inability to determine the status of that particular tumor. Not Done: Radiographic imaging was not performed to evaluate the response. iCR, iPR, and iPD required confirmation by a consecutive assessment at least 4 weeks after first documentation. | The efficacy analysis set included all enrolled participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab, excluding participants with locoregionally advanced disease with a recurrence < 3 months after prior platinum-containing curatively intended multimodal therapy. | Posted | Count of Participants | Participants | Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks. |
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| Secondary | Duration of Confirmed Response | Duration of response (iDOR) per irRECIST was defined as the time from the date of an initial response of iCR or iPR that was subsequently confirmed to the earlier of a participant overall response of iPD or death. Participants who did not end their response at the time of analysis were censored at their last evaluable tumor assessment. | Enrolled participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab, excluding participants with locoregionally advanced disease with a recurrence < 3 months after prior platinum-containing curatively intended multimodal therapy, with a best response of iCR or iPR. | Posted | Median | 95% Confidence Interval | months | Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks. |
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| Secondary | Disease Control Rate | Disease control rate (iDCR) was defined as the percentage of participants with a best overall response of iCR or iPR or iSD assessed by the investigator using irRECIST. Complete response (iCR): Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment no less than 4 weeks from the date first documented was required. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial response (iPR): Decrease in tumor burden ≥ 30% relative to baseline. Confirmation by a consecutive assessment at least 4 weeks after first documentation required. Stable disease (iSD): Neither sufficient shrinkage to qualify for iCR or iPR nor sufficient increase to qualify for iPD. Analyses are presented below for both the unconfirmed and confirmed results. | The efficacy analysis set included all enrolled participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab, excluding participants with locoregionally advanced disease with a recurrence < 3 months after prior platinum-containing curatively intended multimodal therapy. | Posted | Number | 95% Confidence Interval | percentage of participants | Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks. |
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| Secondary | Progression Free Survival | Progression-free survival (iPFS) per irRECIST was defined as the interval from first dose to the earlier of a participant overall response of iPD or death from any cause; otherwise, iPFS was censored at the last evaluable tumor assessment. The initial date of an iPD that was consecutively confirmed was used. | The efficacy analysis set included all enrolled participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab, excluding participants with locoregionally advanced disease with a recurrence < 3 months after prior platinum-containing curatively intended multimodal therapy. | Posted | Median | 95% Confidence Interval | months | Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks. |
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| Secondary | Overall Survival | Overall survival (OS) was defined as the interval from first dose to the event of death from any cause; otherwise, OS was censored at the date the participant was last known to be alive. | The efficacy analysis set included all enrolled participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab, excluding participants with locoregionally advanced disease with a recurrence < 3 months after prior platinum-containing curatively intended multimodal therapy. | Posted | Median | 95% Confidence Interval | months | Up to the primary analysis data cutoff date of 02 November 2017; median (minimum, maximum) time on follow-up was 14.36 (1.4, 67.0) weeks. |
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| Secondary | Number of Participants With Adverse Events | The severity of adverse events was assessed by the investigator according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, and based on the following scale: Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, Grade 5 = death. A serious adverse event is an AE that met at least 1 of the following serious criteria:
| All enrolled participants who received at least 1 dose of talimogene laherparepvec or pembrolizumab. | Posted | Count of Participants | Participants | From first dose of study drug to 30 days after last dose; the median (range) duration of treatment was 5.6 (0.1 to 75.3) weeks for talimogene laherparepvec and 6.1 (0.1, 105.3) weeks for pembrolizumab. |
|
From first dose of study drug to 30 days after last dose; the median (range) duration of treatment was 5.6 (0.1 to 75.3) weeks for talimogene laherparepvec and 6.1 (0.1, 105.3) weeks for pembrolizumab.
Serious adverse event and other adverse events are reported for all participants who received at least one dose of study drug.
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 | Talimogene Laherparepvec + Pembrolizumab | Talimogene laherparepvec was administered by intralesional injection into injectable cutaneous, subcutaneous, and nodal lesions at an initial dose of 10⁶ plaque-forming units (PFU) per mL on day 1 followed by a dose of 10⁸ PFU/mL every 3 weeks (Q3W) thereafter. Pembrolizumab was administered by intravenous infusion at a dose of 200 mg Q3W. Participants were treated until complete response, no injectable lesions, confirmed disease progression, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. | 29 | 36 | 26 | 36 | 33 | 36 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dysphagia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Odynophagia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Chills | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| General physical health deterioration | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Mucosal haemorrhage | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pain | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hepatitis | Hepatobiliary disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Localised infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Pneumonia | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Staphylococcal infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Tracheitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Wound infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Infusion related reaction | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Toxicity to various agents | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Tracheal obstruction | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Tracheostomy malfunction | Injury, poisoning and procedural complications | MedDRA 23.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypercalcaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Squamous cell carcinoma of head and neck | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Delirium | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pneumonia aspiration | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Respiratory arrest | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Stridor | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Eczema | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Arterial haemorrhage | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Wound infection bacterial | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Euglycaemic diabetic ketoacidosis | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Cerebral venous sinus thrombosis | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypotension | Vascular disorders | MedDRA 23.0 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Ear pain | Ear and labyrinth disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypothyroidism | Endocrine disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dysphagia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Odynophagia | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Oral pain | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Stomatitis | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Asthenia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Face oedema | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Influenza like illness | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Injection site pain | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Lower respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Oral candidiasis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Skin infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Body temperature increased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Decreased appetite | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Tumour pain | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 23.0 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Confusional state | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Haemoptysis | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Orthopnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA 23.0 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 23.0 | Systematic Assessment |
| |
| Weight decreased | Investigations | MedDRA 23.0 | Systematic Assessment |
| |
| Increased bronchial secretion | Respiratory, thoracic and mediastinal disorders | MedDRA 23.0 | 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 | Jul 15, 2020 | Aug 13, 2021 | SAP_002.pdf |
| ID | Term |
|---|---|
| D000077195 | Squamous Cell Carcinoma of Head and Neck |
| ID | Term |
|---|---|
| D002294 | Carcinoma, Squamous Cell |
| D002277 | Carcinoma |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006258 | Head and Neck Neoplasms |
| D009371 | Neoplasms by Site |
Not provided
Not provided
| ID | Term |
|---|---|
| C000629782 | talimogene laherparepvec |
| C582435 | pembrolizumab |
Not provided
Not provided
Not provided
| Unknown or Not Reported |
|
| Black (or African American) |
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| Native Hawaiian or Other Pacific Islander |
|
| White |
|
| Other |
|
| Unknown |
|
| Oral Cavity |
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| Hypopharynx |
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