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Pembrolizumab With Talimogene Laherparepvec or Placebo in Unresected Melanoma (MASTERKEY-265)

Primary Purpose

Melanoma

Status

Terminated

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Talimogene Laherparepvec

Pembrolizumab

Placebo

About this trial

This is an interventional treatment trial for Melanoma focused on measuring Talimogene Laherparepvec, pembrolizumab, KEYNOTE-034, MASTERKEY-265

Eligibility Criteria

18 Years - 95 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria:

Age ≥ 18 years with histologically confirmed diagnosis of melanoma and stage IIIB to IVM1c for whom surgery is not recommended.
Subjects must have measurable disease and be a candidate for intralesional therapy administration into cutaneous, subcutaneous, or nodal lesions.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Adequate hematologic, hepatic, renal, and coagulation function.
Subjects with serine/threonine protein kinase B-Raf V600 (BRAFV600) wild-type tumors must not have received any prior systemic anticancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy given in a non-adjuvant setting for unresectable stage IIIB to IVM1c melanoma.
Subjects with B-Raf V600 (BRAFV600) mutated tumors who have received prior BRAF inhibitor therapy either alone or in combination with mitogen-activated protein kinase kinase (MEK) inhibitor as their only prior systemic therapy are eligible.
Subjects who received prior adjuvant therapy for melanoma will not be excluded (including, but not limited to, interferon, ipilimumab, limb infusion/perfusion, or use of investigational agents in the adjuvant setting) with the exception that prior adjuvant therapy with inhibitors of programmed cell death-1 (PD-1) or programmed cell death ligand 1 (PD-L1) is not allowed. However, if the subject received adjuvant therapy, the subject must have completed therapy at least 28 days prior to enrollment.
Subjects must have a tumor sample that is adequate for PD-L1 assessment prior to randomization.

Key Exclusion Criteria:

Subjects must not have clinically active cerebral metastases.
Subjects must not have primary uveal or mucosal melanoma, history or evidence of melanoma associated with immunodeficiency states or history of other malignancy within the past 3 years.
Subjects may not have been previously treated with talimogene laherparepvec, any other oncolytic virus, pembrolizumab, or any other inhibitor of PD-1, PD-L1, or PD-L2.
Subjects must not have history or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, other symptomatic autoimmune disease, documented history of autoimmune disease or syndrome requiring systemic treatment in the past 2 years (ie, with use of disease modifying agents, steroids or immunosuppressive agents) except vitiligo or resolved childhood asthma/atopy, or evidence of clinically significant immunosuppression.
Subjects must not have active herpetic skin lesions or prior complications of herpetic infection and must not require intermittent or chronic treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Experimental

Arm Label

Phase 1b: Talimogene Laherparepvec + Pembrolizumab

Phase 3 : Placebo + Pembrolizumab

Phase 3: Talimogene Laherparepvec + Pembrolizumab

Arm Description

Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ plaque-forming units (PFU)/mL by intralesional injection. Subsequent doses of talimogene laherparepvec at up to 4 mL of 10⁸ PFU/mL began 3 weeks after the first dose and were administered every 2 weeks until disappearance of injectable lesions, complete response (CR), confirmed disease progression (PD) per modified Immune-related Response Criteria (irRC), intolerance of study treatment, 24 months from the date of the first dose of pembrolizumab, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 2 weeks starting at the time of the third dose of talimogene laherparepvec (week 6) until confirmed PD per modified irRC, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first.

Participants received up to 4 mL placebo to talimogene laherparepvec by intralesional injection on day 1 of week 0. Subsequent doses of placebo (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, complete response per modified Immune-related Response Criteria simulating Response Evaluation Criteria in Solid Tumors (irRC-RECIST) (iCR), confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of placebo, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first.

Participants received talimogene laherparepvec at an initial dose of up to 4 mL 10⁶ PFU/mL by intralesional injection on day 1. Subsequent doses of talimogene laherparepvec at 10⁸ PFU/mL (up to 4 mL) began 3 weeks after the first dose and were administered every 2 weeks until the fifth injection of talimogene laherparepvec (week 9), and then synchronously with pembrolizumab thereafter every 3 weeks until disappearance of injectable lesions, iCR, confirmed iPD per modified irRC-RECIST, intolerance of study treatment, 24 months from the date of the first dose of talimogene laherparepvec, or end of study, whichever occurred first. Participants also received 200 mg pembrolizumab administered intravenously every 3 weeks starting on day 1 of week 0, until confirmed iPD per modified irRC-RECIST, treatment intolerance, 24 months from the first dose, or end of study, whichever occurred first.

Outcomes

Primary Outcome Measures

Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)

A DLT was defined as any toxicity related to study drug which met any of the following criteria based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.0: Grade 4 non-hematologic toxicity. Grade 3 or higher pneumonitis. Grade 3 non-hematologic toxicity lasting > 3 days despite optimal supportive care, excluding grade 3 fatigue. Any grade 3 or higher non-hematologic laboratory value if medical intervention was required, or the abnormality lead to hospitalization, or the abnormality persisted for > 1 week. Febrile neutropenia grade 3 or grade 4. Thrombocytopenia < 25 x 10^9/L if associated with a bleeding event which does not result in hemodynamic instability but required an elective platelet infusion, or a life-threatening bleeding event which resulted in urgent intervention and admission to intensive care unit. Grade 5 toxicity (ie, death). Any other intolerable toxicity leading to permanent discontinuation of talimogene laherparepvec or pembrolizumab.

Phase 3: Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) Assessed Using Modified RECIST 1.1

PFS per modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 is defined as the interval from randomization to the earlier event of progressive disease (PD) per modified RECIST 1.1 or death from any cause. PD: Increase in size of target lesions from nadir by ≥ 20% and ≥ 5 mm absolute increase above nadir, or the appearance of a new lesion. Median PFS was calculated using the Kaplan-Meier method. Participants without an event were censored at their last evaluable tumor assessment if available; otherwise on their randomization date. The primary analysis of PFS was specified to be conducted when 407 PFS events had occurred (data cut-off date 02 March 2020).

Phase 3: Overall Survival

Overall survival (OS) is defined as the interval from randomization to death from any cause. Median overall survival was calculated using the Kaplan-Meier method. Participants without an event were censored at their last known alive date.

Secondary Outcome Measures

Phase 1b: Objective Response Rate (ORR)

ORR is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) using the modified Immune-related Response Criteria (irRC), by Investigator assessment. CR was defined as the disappearance of all lesions; PR was defined as a decrease in tumor area ≥ 50% relative to baseline, response must have been confirmed by a second, consecutive assessment at least 4 weeks apart. Radiographic imaging for assessment of lesions was performed using computed tomography (CT), positron emission tomography (PET), magnetic resonance imaging (MRI), or ultrasound. Clinical measurement of cutaneous, subcutaneous, and palpable nodal tumor lesions was conducted with calipers.

Phase 1b: Best Overall Response (BOR)

Best overall response is defined as the best overall visit response in the following order: CR, PR, stable disease (SD), progressive disease (PD), or unevaluable (UE), based on investigator assessment using the modified irRC up to the start of any subsequent anti-cancer therapy. CR was defined as the disappearance of all lesions; PR was defined as a decrease in tumor area ≥ 50% relative to baseline; PD was defined as an increase in tumor area ≥ 25% relative to nadir; and SD was defined as any outcome not meeting the criteria for response or PD with ≥ 77 days elapsed after enrollment. Responses and PD must have been confirmed by a second, consecutive assessment at least 4 weeks apart.

Phase 1b: Durable Response Rate (DRR)

DRR is defined as the percentage of participants with a best overall response of CR or PR using the modified irRC per Investigator assessment with a duration of response of at least 6 months. CR was defined as the disappearance of all lesions; PR was defined as a decrease in tumor area ≥ 50% relative to baseline, response must have been confirmed by a second, consecutive assessment at least 4 weeks apart.

Phase 1b: Duration of Response (DOR)

Duration of response (DOR) is defined as the time from the date of an initial response (CR or PR) that is subsequently confirmed to the earlier of confirmed PD or death. Participants who had not ended their response at the time of analysis were censored at their last evaluable tumor assessment before start of the first subsequent anticancer therapy. CR was defined as the disappearance of all lesions; PR was defined as a decrease in tumor area ≥ 50% relative to baseline; PD was defined as an increase in tumor area ≥ 25% relative to nadir. Response and PD must have been confirmed by a second, consecutive assessment at least 4 weeks apart.

Phase 1b: Disease Control Rate (DCR)

DCR is defined as the percentage of participants with a best overall response of CR, PR, or SD using the modified irRC per Investigator assessment. CR was defined as the disappearance of all lesions; PR was defined as a decrease in tumor area ≥ 50% relative to baseline, response must have been confirmed by a second, consecutive assessment at least 4 weeks apart; and SD was defined as any outcome not meeting the criteria for response or PD with ≥ 84 days elapsed after enrollment.

Phase 1b: Progression-free Survival (PFS)

Progression-free survival is defined as the time from first dose to the earlier event of confirmed PD per modified irRC or death from any cause. PFS was estimated using the Kaplan-Meier method. Participants without an event were censored at their last evaluable tumor assessment.

Phase 1b: Overall Survival (OS)

Overall survival is defined as the interval from first dose to death from any cause. OS was estimated using the Kaplan-Meier method. Participants without an event were censored at their last known alive date.

Phase 3: Complete Response Rate Assessed Using Modified irRC-RECIST (iCRR)

Complete response rate per modified Immune-related Response Criteria (irRC) simulating RECIST 1.1 (irRC-RECIST) is defined as the percentage of participants with a best overall response of complete response assessed using the modified irRC-RECIST (iCR) evaluated by blinded independent central review. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment at least 4 weeks after the criteria were first met. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Modifications to the irRC-RECIST 1.1 included an increase in the total number of target lesions and new measurable lesions to 10 with a maximum of 5 target lesions per organ, and target lesions must have been measurable by CT or MRI only.

Phase 3: Progression Free Survival Assessed Using Modified irRC-RECIST (iPFS)

PFS per modified irRC-RECIST is defined as the interval from randomization to the earlier event of progressive disease assessed by modified irRC-RECIST (iPD) evaluated by blinded independent central review, or death from any cause. iPD: Increase in tumor burden ≥ 20% and at least 5 mm absolute increase relative to nadir (minimum recorded tumor burden) confirmed by a repeat, consecutive assessment at least 4 weeks after the initial detection. Median iPFS was calculated using the Kaplan-Meier method. Participants without an event were censored at their last evaluable tumor assessment if available; otherwise on their randomization date. The primary analysis of iPFS was specified to be conducted when 256 iPFS events had occurred (data cut-off date 29 September 2020).

Phase 3: Overall Survival Excluding Stage IVM1c Participants

Overall survival is defined as the interval from randomization to death from any cause. Median OS was calculated using the Kaplan-Meier method. Participants without an event were censored at the last known alive date.

Phase 3: Objective Response Rate Assessed Using Modified RECIST 1.1

ORR is defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) assessed using modified RECIST version 1.1, evaluated by blinded independent central review. CR was defined as the disappearance of all lesions except lymph node short axis < 10 mm; PR was defined as a ≥ 30% reduction in sum of diameters in target lesions. Confirmation of CR or PR was not required. Modifications to conventional RECIST 1.1 included the following: target lesions were measurable on CT or MRI; otherwise, they were considered as nontarget lesions. A maximum of 10 target lesions was allowed with up to 5 per organ.

Phase 3: Best Overall Response Assessed Using Modified RECIST 1.1

BOR is defined as the best overall visit response up to and including the first overall visit response of PD in the following order: CR, PR, SD, non-CR/Non-PD (NN), PD or UE per modified RECIST 1.1, evaluated by BICR. CR: Disappearance of all lesions except lymph node short axis < 10 mm; PR: ≥ 30% reduction in sum of diameters in target lesions. Confirmation of CR or PR was not required; NN: Persistence of ≥ 1 non-target lesions and/or maintenance of tumor marker level above normal limits; SD: Neither sufficient shrinkage of target lesions to qualify for CR or PR nor sufficient increase to qualify for PD and ≥ 84 days from randomization; PD: Increase from nadir by ≥ 20% or ≥ 5 mm of target lesions or any new lesion; Missing: No postbaseline assessment, or assessments on or after the start of first subsequent anticancer therapy, including complete or partial removal/reduction of any target lesion which contained melanoma on pathology evaluation or pathology results were unknown.

Phase 3: Durable Response Rate (DRR) Assessed Using Modified RECIST 1.1

DRR is defined as the percentage of participants with a CR or PR per modified RECIST 1.1 evaluated by blinded independent central review, with a duration of response of ≥ 6 months. CR was defined as the disappearance of all lesions except lymph node short axis < 10 mm; PR was defined as a ≥ 30% reduction in sum of diameters in target lesions. Confirmation of CR or PR was not required.

Phase 3: Duration of Response (DOR) Assessed Using Modified RECIST 1.1

Duration of response (DOR) is defined as the time from the date of an initial response of CR or PR to the earlier of PD per modified RECIST 1.1, or death. Participants who had not ended their response at the time of analysis were censored at their last evaluable tumor assessment date before start of the first subsequent anticancer therapy. CR was defined as the disappearance of all lesions except lymph node short axis < 10 mm; PR was defined as a ≥ 30% reduction in sum of diameters in target lesions. Confirmation of CR or PR was not required. PD was defined as an increase from nadir by ≥ 20% or ≥ 5 mm absolute increase above nadir of target lesions or appearance of any new lesion.

Phase 3: Disease Control Rate (DCR) Assessed Using RECIST 1.1

Disease control rate (DCR) per modified RECIST 1.1 is defined as the percentage of participants with a best overall response of CR, PR or SD evaluated by blinded independent central review. CR was defined as the disappearance of all lesions except lymph node short axis < 10 mm; PR was defined as a ≥ 30% reduction in sum of diameters in target lesions. Confirmation of CR or PR was not required. SD was defined as neither sufficient shrinkage of target lesions to qualify for CR or PR nor sufficient increase to qualify for PD with ≥ 84 days elapsed after randomization.

Phase 3: Objective Response Rate Assessed Using Modified irRC-RECIST (iORR)

Objective response rate per modified irRC-RECIST is defined as the percentage of participants with a best overall response of iCR or partial response assessed using modified irRC-RECIST (iPR) evaluated by blinded independent central review. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment at least 4 weeks from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. iPR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation. Modifications to the irRC-RECIST 1.1 included an increase in the total number of target lesions and new measurable lesions to 10 with a maximum of 5 target lesions per organ, and target lesions must be measurable by CT or MRI only.

Phase 3: Best Overall Response Assessed Using Modified irRC-RECIST

BOR is defined as the best overall visit response in the following order: iCR, iPR, stable disease per modified irRC-RECIST (iSD), iPD, or UE per modified irRC-RECIST (iUE), evaluated by BICR. iCR: Disappearance of all lesions confirmed by consecutive assessment ≥ 4 weeks from the date first documented. Reduction of any pathological lymph node to <10 mm. iPR: Decrease in tumor burden ≥ 30% relative to baseline confirmed ≥ 4 weeks after first documentation. iPD: Increase in tumor burden ≥ 20 % and at least 5 mm absolute increase relative to nadir confirmed ≥ 4 weeks from initial detection. iSD: Neither sufficient shrinkage to qualify for iCR or iPR nor sufficient increase to qualify for iPD and ≥ 84 days from randomization. Missing: No postbaseline assessment, or assessments after start of first subsequent anticancer therapy, including complete or partial removal/reduction of any target lesion which contained melanoma on pathology evaluation or pathology results were unknown.

Phase 3: Durable Response Rate Assessed Using Modified irRC-RECIST (iDRR)

Durable response rate per modified irRC-RECIST is defined as the percentage of participants with a best overall response of iCR or iPR per modified irRC-RECIST evaluated by blinded independent central review with a duration of response ≥ 6 months. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment at least 4 weeks from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. iPR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation.

Phase 3: Duration of Response Assessed Using Modified irRC-RECIST (iDOR)

Duration of response per modified irRC-RECIST is defined as the time from the date of an initial response of iCR or iPR that was subsequently confirmed to the earlier of iPD per modified irRC-RECIST evaluated by blinded independent central review, or death. Participants who had not ended their response at the time of analysis were censored at their last evaluable tumor assessment date before the start of the first subsequent anticancer therapy. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment at least 4 weeks from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. iPR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation.

Phase 3: Disease Control Rate Assessed Using Modified irRC-RECIST (iDCR)

Disease control rate per modified irRC-RECIST is defined as the percentage of participants with a best overall response of iCR, iCR, or iSD assessed using modified irRC-RECIST evaluated by blinded independent central review. iCR: Disappearance of all lesions (whether measurable or not and whether baseline or new) and confirmation by a repeat, consecutive assessment at least 4 weeks from the date first documented. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. iPR: Decrease in tumor burden ≥ 30% relative to baseline confirmed by a consecutive assessment at least 4 weeks after first documentation. iSD: Neither sufficient shrinkage to qualify for iCR or iPR nor sufficient increase to qualify for iPD with ≥ 84 days elapsed after randomization.

Phase 3: Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL) Score

The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30 (EORTC QLQ-C30) is a 30-question tool used to assess the overall quality of life in cancer patients. It consists of 15 domains: 1 global health status/quality of life scale, 5 functional scales, and 9 symptom scales/items. The global health/QoL scale consists of 2 questions that ask participants to rate their overall health and overall quality of life during the past week on a scale from 1 (very poor) to 7 (excellent). The GHS/QoL subscale score was derived as the mean of each score then transformed to a scale from 0 to 100 where higher scores represent a better health status and a positive change from baseline indicates improvement. The overall change from baseline (calculated from all on-treatment visits) was calculated using a restricted maximum likelihood-based mixed model for repeated measures (MMRM) (see model details in statistical analysis section).

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

An adverse event (AE) is any untoward medical occurrence in a clinical trial subject, including worsening of a pre-existing medical condition. The event does not necessarily have a causal relationship with study treatment. TEAEs include AEs from the first dose of study drug to 30 days after the last dose. A serious adverse event (SAE) is an AE that met at least 1 of the following criteria: fatal life threatening required in-patient hospitalization or prolongation of existing hospitalization resulted in persistent or significant disability/incapacity congenital anomaly/birth defect other medically important serious event. Treatment-emergent SAEs are any SAE occurring from first dose of study drug through 90 days after the last dose or 30 days after the last dose if new anticancer therapy was started, whichever was earlier. AEs were graded for severity using CTCAE version 4.0, where Grade 1 = Mild; Grade 2 = Moderate; Grade 3 = Severe; Grade 4 = Life-threatening; Grade 5 = Fatal.

Full Information

NCT ID

NCT02263508

First Posted

September 26, 2014

Last Updated

November 10, 2022

Sponsor

Amgen

Collaborators

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT02263508

Brief Title

Pembrolizumab With Talimogene Laherparepvec or Placebo in Unresected Melanoma

Acronym

MASTERKEY-265

Official Title

A Phase 1b/3, Multicenter, Trial of Talimogene Laherparepvec in Combination With Pembrolizumab (MK-3475) for Treatment of Unresectable Stage IIIB to IVM1c Melanoma (MASTERKEY-265)

Study Type

Interventional

2. Study Status

Record Verification Date

November 2022

Overall Recruitment Status

Terminated

Study Start Date

December 8, 2014 (Actual)

Primary Completion Date

March 11, 2021 (Actual)

Study Completion Date

March 11, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Amgen

Collaborators

Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

The primary objectives of the Phase 1b part of the study are to evaluate the safety, as assessed by incidence of dose limiting toxicity (DLT), of talimogene laherparepvec in combination with pembrolizumab in adults with previously untreated, unresectable, stage IIIB to IVM1c melanoma. The primary objective of Phase 3 are to evaluate the efficacy of talimogene laherparepvec with pembrolizumab versus placebo with pembrolizumab, as assessed by progression-free survival (PFS) (response evaluation by blinded independent central review using modified Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) and overall survival (OS).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Melanoma

Keywords

Talimogene Laherparepvec, pembrolizumab, KEYNOTE-034, MASTERKEY-265

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Model Description

Phase 1b was an open-label, single-arm study. Phase 3 was a randomized, double-blind, placebo-controlled study design.

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

713 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Phase 1b: Talimogene Laherparepvec + Pembrolizumab

Arm Type

Experimental

Arm Description

Arm Title

Phase 3 : Placebo + Pembrolizumab

Arm Type

Placebo Comparator

Arm Description

Arm Title

Phase 3: Talimogene Laherparepvec + Pembrolizumab

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Talimogene Laherparepvec

Other Intervention Name(s)

IMLYGIC®, OncoVEX^GM-CSF, T-VEC

Intervention Description

Talimogene laherparepvec administered by intratumoral injection

Intervention Type

Drug

Intervention Name(s)

Pembrolizumab

Other Intervention Name(s)

MK-3475, Keytruda®

Intervention Description

Administered at a dose of 200 mg as an intravenous infusion over approximately 30 minutes.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Administered by intratumoral injection

Primary Outcome Measure Information:

Title

Phase 1b: Number of Participants With Dose-limiting Toxicities (DLTs)

Description

Time Frame

The DLT evaluation period was 6 weeks from the initial administration of pembrolizumab (week 6 to 12).

Title

Phase 3: Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) Assessed Using Modified RECIST 1.1

Description

Time Frame

From randomization until the data-cut-off date of 02 March 2020; median (range) time on follow-up was 25.5 (0.6, 44.7) months in the Placebo + Pembrolizumab arm and 25.6 (0.3, 45.8) months in the Talimogene Laherparepvec + Pembrolizumab arm.

Title

Phase 3: Overall Survival

Description

Time Frame

From randomization until the end of study; median (range) time on follow-up was 34.8 (0.6, 58.3) months in the Placebo + Pembrolizumab arm and 36.8 (0.3, 58.4) months in the Talimogene Laherparepvec + Pembrolizumab arm.

Secondary Outcome Measure Information:

Title

Phase 1b: Objective Response Rate (ORR)

Description

Time Frame

Tumor assessments were performed at week 6 (prior to initiation of pembrolizumab), week 18, and every 12 weeks thereafter until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 58.6 (1.4, 61.6) months.

Title

Phase 1b: Best Overall Response (BOR)

Description

Time Frame

Title

Phase 1b: Durable Response Rate (DRR)

Description

Time Frame

Title

Phase 1b: Duration of Response (DOR)

Description

Time Frame

Title

Phase 1b: Disease Control Rate (DCR)

Description

Time Frame

Title

Phase 1b: Progression-free Survival (PFS)

Description

Time Frame

From first dose until the end of study; median (range) time on follow-up was 70.6 (1.4, 74.5) months.

Title

Phase 1b: Overall Survival (OS)

Description

Time Frame

From first dose until the end of study; median (range) time on follow-up was 70.6 (1.4, 74.5) months.

Title

Phase 3: Complete Response Rate Assessed Using Modified irRC-RECIST (iCRR)

Description

Time Frame

Tumor assessments were performed every 12 weeks after initiation of treatment until confirmed PD or start of new anticancer treatment; median (range) time on follow-up was 30.6 (0.6, 53.0) months and 31.4 (0.3, 52.5) months in each group, respectively.

Title

Phase 3: Progression Free Survival Assessed Using Modified irRC-RECIST (iPFS)

Description

Time Frame

From randomization until the data cut-off date of 29 September 2020; median time on follow-up was 30.6 (0.6, 53.0) months in the Placebo + Pembrolizumab arm and 31.4 (0.3, 52.5) months in the Talimogene Laherparepvec + Pembrolizumab arm.

Title

Phase 3: Overall Survival Excluding Stage IVM1c Participants

Description

Time Frame

Title

Phase 3: Objective Response Rate Assessed Using Modified RECIST 1.1

Description

Time Frame

Title

Phase 3: Best Overall Response Assessed Using Modified RECIST 1.1

Description

Time Frame

Title

Phase 3: Durable Response Rate (DRR) Assessed Using Modified RECIST 1.1

Description

Time Frame

Title

Phase 3: Duration of Response (DOR) Assessed Using Modified RECIST 1.1

Description

Time Frame

Title

Phase 3: Disease Control Rate (DCR) Assessed Using RECIST 1.1

Description

Time Frame

Title

Phase 3: Objective Response Rate Assessed Using Modified irRC-RECIST (iORR)

Description

Time Frame

Title

Phase 3: Best Overall Response Assessed Using Modified irRC-RECIST

Description

Time Frame

Title

Phase 3: Durable Response Rate Assessed Using Modified irRC-RECIST (iDRR)

Description

Time Frame

Title

Phase 3: Duration of Response Assessed Using Modified irRC-RECIST (iDOR)

Description

Time Frame

Title

Phase 3: Disease Control Rate Assessed Using Modified irRC-RECIST (iDCR)

Description

Time Frame

Title

Phase 3: Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Core Module (EORTC QLQ-C30) Global Health Status (GHS)/Quality of Life (QOL) Score

Description

Time Frame

Baseline and day 1 of weeks 3, 6, 9, 12, then every 6 weeks until end of study treatment; median (range) duration of treatment was 39.0 (0.1, 107.3) weeks in Placebo + Pembrolizumab and 54.1 (0.1, 109.6) weeks in Talimogene Laherparepvec + Pembrolizumab.

Title

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Description

Time Frame

From first dose to 30 days after last dose (90 days for SAEs); median (range) duration was 48 (5.1, 110.1) weeks in Phase 1b, 39 (0.1, 107.3) weeks in Placebo + Pembrolizumab and 56 (0.1, 109.6) weeks in Phase 3 Talimogene Laherparepvec + Pembrolizumab.

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

95 Years

Accepts Healthy Volunteers

Eligibility Criteria

Key Inclusion Criteria: Age ≥ 18 years with histologically confirmed diagnosis of melanoma and stage IIIB to IVM1c for whom surgery is not recommended. Subjects must have measurable disease and be a candidate for intralesional therapy administration into cutaneous, subcutaneous, or nodal lesions. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Adequate hematologic, hepatic, renal, and coagulation function. Subjects with serine/threonine protein kinase B-Raf V600 (BRAFV600) wild-type tumors must not have received any prior systemic anticancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy given in a non-adjuvant setting for unresectable stage IIIB to IVM1c melanoma. Subjects with B-Raf V600 (BRAFV600) mutated tumors who have received prior BRAF inhibitor therapy either alone or in combination with mitogen-activated protein kinase kinase (MEK) inhibitor as their only prior systemic therapy are eligible. Subjects who received prior adjuvant therapy for melanoma will not be excluded (including, but not limited to, interferon, ipilimumab, limb infusion/perfusion, or use of investigational agents in the adjuvant setting) with the exception that prior adjuvant therapy with inhibitors of programmed cell death-1 (PD-1) or programmed cell death ligand 1 (PD-L1) is not allowed. However, if the subject received adjuvant therapy, the subject must have completed therapy at least 28 days prior to enrollment. Subjects must have a tumor sample that is adequate for PD-L1 assessment prior to randomization. Key Exclusion Criteria: Subjects must not have clinically active cerebral metastases. Subjects must not have primary uveal or mucosal melanoma, history or evidence of melanoma associated with immunodeficiency states or history of other malignancy within the past 3 years. Subjects may not have been previously treated with talimogene laherparepvec, any other oncolytic virus, pembrolizumab, or any other inhibitor of PD-1, PD-L1, or PD-L2. Subjects must not have history or evidence of symptomatic autoimmune pneumonitis, glomerulonephritis, vasculitis, other symptomatic autoimmune disease, documented history of autoimmune disease or syndrome requiring systemic treatment in the past 2 years (ie, with use of disease modifying agents, steroids or immunosuppressive agents) except vitiligo or resolved childhood asthma/atopy, or evidence of clinically significant immunosuppression. Subjects must not have active herpetic skin lesions or prior complications of herpetic infection and must not require intermittent or chronic treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Organizational Affiliation

Amgen

Official's Role

Study Director

Facility Information:

Facility Name

Research Site

City

Birmingham

State/Province

Alabama

ZIP/Postal Code

35243

Country

United States

Facility Name

Research Site

City

Mobile

State/Province

Alabama

ZIP/Postal Code

36608

Country

United States

Facility Name

Research Site

City

Beverly Hills

State/Province

California

ZIP/Postal Code

90211

Country

United States

Facility Name

Research Site

City

Duarte

State/Province

California

ZIP/Postal Code

91010

Country

United States

Facility Name

Research Site

City

Encinitas

State/Province

California

ZIP/Postal Code

92024

Country

United States

Facility Name

Research Site

City

La Jolla

State/Province

California

ZIP/Postal Code

92037

Country

United States

Facility Name

Research Site

City

Los Angeles

State/Province

California

ZIP/Postal Code

90024

Country

United States

Facility Name

Research Site

City

Los Angeles

State/Province

California

ZIP/Postal Code

90025

Country

United States

Facility Name

Research Site

City

Riverside

State/Province

California

ZIP/Postal Code

92505

Country

United States

Facility Name

Research Site

City

San Francisco

State/Province

California

ZIP/Postal Code

94115

Country

United States

Facility Name

Research Site

City

San Francisco

State/Province

California

ZIP/Postal Code

94117

Country

United States

Facility Name

Research Site

City

Santa Monica

State/Province

California

ZIP/Postal Code

90404

Country

United States

Facility Name

Research Site

City

Miami Beach

State/Province

Florida

ZIP/Postal Code

33140

Country

United States

Facility Name

Research Site

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

Facility Name

Research Site

City

Orlando

State/Province

Florida

ZIP/Postal Code

32806

Country

United States

Facility Name

Research Site

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30322

Country

United States

Facility Name

Research Site

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

Research Site

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60637

Country

United States

Facility Name

Research Site

City

Louisville

State/Province

Kentucky

ZIP/Postal Code

40202

Country

United States

Facility Name

Research Site

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21237

Country

United States

Facility Name

Research Site

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02215

Country

United States

Facility Name

Research Site

City

Detroit

State/Province

Michigan

ZIP/Postal Code

48201

Country

United States

Facility Name

Research Site

City

Fridley

State/Province

Minnesota

ZIP/Postal Code

55432

Country

United States

Facility Name

Research Site

City

Saint Louis

State/Province

Missouri

ZIP/Postal Code

63110-1093

Country

United States

Facility Name

Research Site

City

Hackensack

State/Province

New Jersey

ZIP/Postal Code

07601

Country

United States

Facility Name

Research Site

City

Buffalo

State/Province

New York

ZIP/Postal Code

14263

Country

United States

Facility Name

Research Site

City

New York

State/Province

New York

ZIP/Postal Code

10016

Country

United States

Facility Name

Research Site

City

New York

State/Province

New York

ZIP/Postal Code

10032

Country

United States

Facility Name

Research Site

City

New York

State/Province

New York

ZIP/Postal Code

10065

Country

United States

Facility Name

Research Site

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45209

Country

United States

Facility Name

Research Site

City

Cleveland

State/Province

Ohio

ZIP/Postal Code

44195

Country

United States

Facility Name

Research Site

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19107

Country

United States

Facility Name

Research Site

City

Philadelphia

State/Province

Pennsylvania

ZIP/Postal Code

19111

Country

United States

Facility Name

Research Site

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15232

Country

United States

Facility Name

Research Site

City

Germantown

State/Province

Tennessee

ZIP/Postal Code

38138

Country

United States

Facility Name

Research Site

City

Knoxville

State/Province

Tennessee

ZIP/Postal Code

37920

Country

United States

Facility Name

Research Site

City

Nashville

State/Province

Tennessee

ZIP/Postal Code

37232

Country

United States

Facility Name

Research Site

City

Dallas

State/Province

Texas

ZIP/Postal Code

75246

Country

United States

Facility Name

Research Site

City

Murray

State/Province

Utah

ZIP/Postal Code

84107

Country

United States

Facility Name

Research Site

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84112

Country

United States

Facility Name

Research Site

City

Seattle

State/Province

Washington

ZIP/Postal Code

98109-1023

Country

United States

Facility Name

Research Site

City

North Sydney

State/Province

New South Wales

ZIP/Postal Code

2060

Country

Australia

Facility Name

Research Site

City

Waratah

State/Province

New South Wales

ZIP/Postal Code

2298

Country

Australia

Facility Name

Research Site

City

Wollongong

State/Province

New South Wales

ZIP/Postal Code

2500

Country

Australia

Facility Name

Research Site

City

Southport

State/Province

Queensland

ZIP/Postal Code

4215

Country

Australia

Facility Name

Research Site

City

Woolloongabba

State/Province

Queensland

ZIP/Postal Code

4102

Country

Australia

Facility Name

Research Site

City

Woodville South

State/Province

South Australia

ZIP/Postal Code

5011

Country

Australia

Facility Name

Research Site

City

Geelong

State/Province

Victoria

ZIP/Postal Code

3220

Country

Australia

Facility Name

Research Site

City

Heidelberg

State/Province

Victoria

ZIP/Postal Code

3084

Country

Australia

Facility Name

Research Site

City

Melbourne

State/Province

Victoria

ZIP/Postal Code

3000

Country

Australia

Facility Name

Research Site

City

Prahran

State/Province

Victoria

ZIP/Postal Code

3181

Country

Australia

Facility Name

Research Site

City

Murdoch

State/Province

Western Australia

ZIP/Postal Code

6150

Country

Australia

Facility Name

Research Site

City

Graz

ZIP/Postal Code

8036

Country

Austria

Facility Name

Research Site

City

Innsbruck

ZIP/Postal Code

6020

Country

Austria

Facility Name

Research Site

City

Salzburg

ZIP/Postal Code

5020

Country

Austria

Facility Name

Research Site

City

Wien

ZIP/Postal Code

1090

Country

Austria

Facility Name

Research Site

City

Bruxelles

ZIP/Postal Code

1200

Country

Belgium

Facility Name

Research Site

City

Liege

ZIP/Postal Code

4000

Country

Belgium

Facility Name

Research Site

City

Edmonton

State/Province

Alberta

ZIP/Postal Code

T6G 1Z2

Country

Canada

Facility Name

Research Site

City

Kingston

State/Province

Ontario

ZIP/Postal Code

K7L 2V7

Country

Canada

Facility Name

Research Site

City

London

State/Province

Ontario

ZIP/Postal Code

N6A 4L6

Country

Canada

Facility Name

Research Site

City

Ottawa

State/Province

Ontario

ZIP/Postal Code

K1H 8L6

Country

Canada

Facility Name

Research Site

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 2M9

Country

Canada

Facility Name

Research Site

City

Montreal

State/Province

Quebec

ZIP/Postal Code

H3T 1E2

Country

Canada

Facility Name

Research Site

City

Quebec

ZIP/Postal Code

G1R 2J6

Country

Canada

Facility Name

Research Site

City

Brno

ZIP/Postal Code

656 53

Country

Czechia

Facility Name

Research Site

City

Olomouc

ZIP/Postal Code

775 20

Country

Czechia

Facility Name

Research Site

City

Ostrava-Poruba

ZIP/Postal Code

708 52

Country

Czechia

Facility Name

Research Site

City

Praha 10

ZIP/Postal Code

100 34

Country

Czechia

Facility Name

Research Site

City

Praha 2

ZIP/Postal Code

128 08

Country

Czechia

Facility Name

Research Site

City

Praha 8

ZIP/Postal Code

180 81

Country

Czechia

Facility Name

Research Site

City

Helsinki

ZIP/Postal Code

00290

Country

Finland

Facility Name

Research Site

City

Bordeaux Cedex

ZIP/Postal Code

33075

Country

France

Facility Name

Research Site

City

Grenoble Cedex 9

ZIP/Postal Code

38043

Country

France

Facility Name

Research Site

City

Lille

ZIP/Postal Code

59037

Country

France

Facility Name

Research Site

City

Lyon cedex 08

ZIP/Postal Code

69373

Country

France

Facility Name

Research Site

City

Marseille cedex 05

ZIP/Postal Code

13385

Country

France

Facility Name

Research Site

City

Nantes Cedex 1

ZIP/Postal Code

44093

Country

France

Facility Name

Research Site

City

Paris

ZIP/Postal Code

75010

Country

France

Facility Name

Research Site

City

Pierre Benite Cedex

ZIP/Postal Code

69495

Country

France

Facility Name

Research Site

City

Toulouse cedex 9

ZIP/Postal Code

31059

Country

France

Facility Name

Research Site

City

Vandoeuvre les Nancy

ZIP/Postal Code

54511

Country

France

Facility Name

Research Site

City

Berlin

ZIP/Postal Code

10117

Country

Germany

Facility Name

Research Site

City

Dresden

ZIP/Postal Code

01307

Country

Germany

Facility Name

Research Site

City

Erlangen

ZIP/Postal Code

91054

Country

Germany

Facility Name

Research Site

City

Essen

ZIP/Postal Code

45147

Country

Germany

Facility Name

Research Site

City

Hannover

ZIP/Postal Code

30625

Country

Germany

Facility Name

Research Site

City

Heidelberg

ZIP/Postal Code

69120

Country

Germany

Facility Name

Research Site

City

Kiel

ZIP/Postal Code

24105

Country

Germany

Facility Name

Research Site

City

Leipzig

ZIP/Postal Code

04103

Country

Germany

Facility Name

Research Site

City

Mainz

ZIP/Postal Code

55131

Country

Germany

Facility Name

Research Site

City

Mannheim

ZIP/Postal Code

68167

Country

Germany

Facility Name

Research Site

City

München

ZIP/Postal Code

80337

Country

Germany

Facility Name

Research Site

City

Regensburg

ZIP/Postal Code

93053

Country

Germany

Facility Name

Research Site

City

Tübingen

ZIP/Postal Code

72076

Country

Germany

Facility Name

Research Site

City

Würzburg

ZIP/Postal Code

97080

Country

Germany

Facility Name

Research Site

City

Athens

ZIP/Postal Code

11527

Country

Greece

Facility Name

Research Site

City

Athens

ZIP/Postal Code

18547

Country

Greece

Facility Name

Research Site

City

Heraklion - Crete

ZIP/Postal Code

71110

Country

Greece

Facility Name

Research Site

City

Ioannina

ZIP/Postal Code

45500

Country

Greece

Facility Name

Research Site

City

Thessaloniki

ZIP/Postal Code

54622

Country

Greece

Facility Name

Research Site

City

Budapest

ZIP/Postal Code

1122

Country

Hungary

Facility Name

Research Site

City

Pecs

ZIP/Postal Code

7632

Country

Hungary

Facility Name

Research Site

City

Szeged

ZIP/Postal Code

6720

Country

Hungary

Facility Name

Research Site

City

Bergamo

ZIP/Postal Code

24127

Country

Italy

Facility Name

Research Site

City

Brescia

ZIP/Postal Code

25123

Country

Italy

Facility Name

Research Site

City

Meldola FC

ZIP/Postal Code

47014

Country

Italy

Facility Name

Research Site

City

Milano

ZIP/Postal Code

20133

Country

Italy

Facility Name

Research Site

City

Milano

ZIP/Postal Code

20141

Country

Italy

Facility Name

Research Site

City

Siena

ZIP/Postal Code

53100

Country

Italy

Facility Name

Research Site

City

Seoul

ZIP/Postal Code

03722

Country

Korea, Republic of

Facility Name

Research Site

City

Seoul

ZIP/Postal Code

05505

Country

Korea, Republic of

Facility Name

Research Site

City

Amsterdam

ZIP/Postal Code

1066 CX

Country

Netherlands

Facility Name

Research Site

City

Amsterdam

ZIP/Postal Code

1081 HV

Country

Netherlands

Facility Name

Research Site

City

Groningen

ZIP/Postal Code

9713 GZ

Country

Netherlands

Facility Name

Research Site

City

Nijmegen

ZIP/Postal Code

6525 GA

Country

Netherlands

Facility Name

Research Site

City

Bielsko-Biala

ZIP/Postal Code

43-300

Country

Poland

Facility Name

Research Site

City

Bydgoszcz

ZIP/Postal Code

85-796

Country

Poland

Facility Name

Research Site

City

Gdansk

ZIP/Postal Code

80-952

Country

Poland

Facility Name

Research Site

City

Konin

ZIP/Postal Code

62-500

Country

Poland

Facility Name

Research Site

City

Krakow

ZIP/Postal Code

31-501

Country

Poland

Facility Name

Research Site

City

Poznan

ZIP/Postal Code

60-848

Country

Poland

Facility Name

Research Site

City

Poznan

ZIP/Postal Code

61-866

Country

Poland

Facility Name

Research Site

City

Szczecin

ZIP/Postal Code

71-730

Country

Poland

Facility Name

Research Site

City

Warszawa

ZIP/Postal Code

02-781

Country

Poland

Facility Name

Research Site

City

Wroclaw

ZIP/Postal Code

50-368

Country

Poland

Facility Name

Research Site

City

Almada

ZIP/Postal Code

2801-951

Country

Portugal

Facility Name

Research Site

City

Lisboa

ZIP/Postal Code

1099-023

Country

Portugal

Facility Name

Research Site

City

Lisboa

ZIP/Postal Code

1649-035

Country

Portugal

Facility Name

Research Site

City

Porto

ZIP/Postal Code

4200-072

Country

Portugal

Facility Name

Research Site

City

Moscow

ZIP/Postal Code

115478

Country

Russian Federation

Facility Name

Research Site

City

Saint-Petersburg

ZIP/Postal Code

197758

Country

Russian Federation

Facility Name

Research Site

City

Groenkloof

State/Province

Gauteng

ZIP/Postal Code

0181

Country

South Africa

Facility Name

Research Site

City

Johannesburg

State/Province

Gauteng

ZIP/Postal Code

2196

Country

South Africa

Facility Name

Research Site

City

Parktown

State/Province

Gauteng

ZIP/Postal Code

2193

Country

South Africa

Facility Name

Research Site

City

Kraaifontein

ZIP/Postal Code

7570

Country

South Africa

Facility Name

Research Site

City

Pretoria

ZIP/Postal Code

0002

Country

South Africa

Facility Name

Research Site

City

Pretoria

ZIP/Postal Code

0081

Country

South Africa

Facility Name

Research Site

City

Badalona

State/Province

Cataluña

ZIP/Postal Code

08916

Country

Spain

Facility Name

Research Site

City

Barcelona

State/Province

Cataluña

ZIP/Postal Code

08036

Country

Spain

Facility Name

Research Site

City

Valencia

State/Province

Comunidad Valenciana

ZIP/Postal Code

46014

Country

Spain

Facility Name

Research Site

City

Pamplona

State/Province

Navarra

ZIP/Postal Code

31008

Country

Spain

Facility Name

Research Site

City

San Sebastian

State/Province

País Vasco

ZIP/Postal Code

20014

Country

Spain

Facility Name

Research Site

City

Madrid

ZIP/Postal Code

28009

Country

Spain

Facility Name

Research Site

City

Madrid

ZIP/Postal Code

28046

Country

Spain

Facility Name

Research Site

City

Madrid

ZIP/Postal Code

28050

Country

Spain

Facility Name

Research Site

City

Bellinzona

ZIP/Postal Code

6500

Country

Switzerland

Facility Name

Research Site

City

Bern

ZIP/Postal Code

3010

Country

Switzerland

Facility Name

Research Site

City

Geneva 14

ZIP/Postal Code

1211

Country

Switzerland

Facility Name

Research Site

City

Lausanne

ZIP/Postal Code

1011

Country

Switzerland

Facility Name

Research Site

City

Zürich

ZIP/Postal Code

8091

Country

Switzerland

Facility Name

Research Site

City

Birmingham

ZIP/Postal Code

B15 2TH

Country

United Kingdom

Facility Name

Research Site

City

Guildford

ZIP/Postal Code

GU2 7XX

Country

United Kingdom

Facility Name

Research Site

City

Leeds

ZIP/Postal Code

LS9 7TF

Country

United Kingdom

Facility Name

Research Site

City

Leicester

ZIP/Postal Code

LE1 5WW

Country

United Kingdom

Facility Name

Research Site

City

London

ZIP/Postal Code

SE1 9RT

Country

United Kingdom

Facility Name

Research Site

City

London

ZIP/Postal Code

SW3 6JJ

Country

United Kingdom

Facility Name

Research Site

City

Manchester

ZIP/Postal Code

M20 4BX

Country

United Kingdom

Facility Name

Research Site

City

Oxford

ZIP/Postal Code

OX3 7LJ

Country

United Kingdom

Facility Name

Research Site

City

Preston

ZIP/Postal Code

PR2 9HT

Country

United Kingdom

Facility Name

Research Site

City

Southampton

ZIP/Postal Code

SO16 6YD

Country

United Kingdom

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

IPD Sharing Time Frame

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.

IPD Sharing Access Criteria

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.

IPD Sharing URL

https://www.amgen.com/datasharing

Citations:

PubMed Identifier

28886381

Citation

Ribas A, Dummer R, Puzanov I, VanderWalde A, Andtbacka RHI, Michielin O, Olszanski AJ, Malvehy J, Cebon J, Fernandez E, Kirkwood JM, Gajewski TF, Chen L, Gorski KS, Anderson AA, Diede SJ, Lassman ME, Gansert J, Hodi FS, Long GV. Oncolytic Virotherapy Promotes Intratumoral T Cell Infiltration and Improves Anti-PD-1 Immunotherapy. Cell. 2017 Sep 7;170(6):1109-1119.e10. doi: 10.1016/j.cell.2017.08.027. Erratum In: Cell. 2018 Aug 9;174(4):1031-1032.

Results Reference

background

PubMed Identifier

28238174

Citation

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.

Results Reference

background

PubMed Identifier

35998300

Citation

Chesney JA, Ribas A, Long GV, Kirkwood JM, Dummer R, Puzanov I, Hoeller C, Gajewski TF, Gutzmer R, Rutkowski P, Demidov L, Arenberger P, Shin SJ, Ferrucci PF, Haydon A, Hyngstrom J, van Thienen JV, Haferkamp S, Guilera JM, Rapoport BL, VanderWalde A, Diede SJ, Anderson JR, Treichel S, Chan EL, Bhatta S, Gansert J, Hodi FS, Gogas H. Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma. J Clin Oncol. 2023 Jan 20;41(3):528-540. doi: 10.1200/JCO.22.00343. Epub 2022 Aug 23.

Results Reference

background

PubMed Identifier

29896663

Citation

Watanabe D, Goshima F. Oncolytic Virotherapy by HSV. Adv Exp Med Biol. 2018;1045:63-84. doi: 10.1007/978-981-10-7230-7_4.

Results Reference

derived

Links:

URL

http://www.amgentrials.com

Description

AmgenTrials clinical trials website

Learn more about this trial

Pembrolizumab With Talimogene Laherparepvec or Placebo in Unresected Melanoma

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Pembrolizumab With Talimogene Laherparepvec or Placebo in Unresected Melanoma (MASTERKEY-265)

Melanoma

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

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