Pembrolizumab With or Without Talimogene Laherparepvec or Talimogene Laherparepvec Placebo in Unresected Melanoma (KEYNOTE-034)
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ClinicalTrials.gov Identifier: NCT02263508 |
Recruitment Status :
Active, not recruiting
First Posted : October 13, 2014
Last Update Posted : December 22, 2020
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Condition or disease | Intervention/treatment | Phase |
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Melanoma | Drug: talimogene laherparepvec Drug: pembrolizumab (MK-3475) Drug: placebo | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 713 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | Double (Participant, Investigator) |
Primary Purpose: | Treatment |
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/KEYNOTE-034) |
Actual Study Start Date : | December 8, 2014 |
Estimated Primary Completion Date : | July 29, 2022 |
Estimated Study Completion Date : | April 28, 2023 |

Arm | Intervention/treatment |
---|---|
Experimental: Phase 1b;
Phase 1b: talimogene laherparepvec and pembrolizumab (MK-3475)
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Drug: talimogene laherparepvec
Phase 1b: talimogene laherparepvec will be administered by intralesional injection at Day 1, Week -5; then every 2 weeks starting at Day 1, Week -2; Phase 3, Arm 1 talimogene laherparepvec will be administered by intralesional injection at Day 1 Week 0, 3, 5, 7 then every 3 weeks starting at Day 1 Week 9. Drug: pembrolizumab (MK-3475) Phase 1b: pembrolizumab will be administered intravenously every 2 weeks starting at Day 1 Week 0; Phase 3, Arm 1 and Arm 2 pembrolizumab will be administered intravenously on Day 1 Week 0, then every 3 weeks starting at Day 1 Week 3. |
Experimental: Phase 3 Arm 1;
Phase 3 Arm 1: talimogene laherparepvec and pembrolizumab (MK-3475)
|
Drug: talimogene laherparepvec
Phase 1b: talimogene laherparepvec will be administered by intralesional injection at Day 1, Week -5; then every 2 weeks starting at Day 1, Week -2; Phase 3, Arm 1 talimogene laherparepvec will be administered by intralesional injection at Day 1 Week 0, 3, 5, 7 then every 3 weeks starting at Day 1 Week 9. Drug: pembrolizumab (MK-3475) Phase 1b: pembrolizumab will be administered intravenously every 2 weeks starting at Day 1 Week 0; Phase 3, Arm 1 and Arm 2 pembrolizumab will be administered intravenously on Day 1 Week 0, then every 3 weeks starting at Day 1 Week 3. |
Experimental: Phase 3 Arm 2;
Phase 3 Arm 2: placebo and pembrolizumab (MK-3475)
|
Drug: pembrolizumab (MK-3475)
Phase 1b: pembrolizumab will be administered intravenously every 2 weeks starting at Day 1 Week 0; Phase 3, Arm 1 and Arm 2 pembrolizumab will be administered intravenously on Day 1 Week 0, then every 3 weeks starting at Day 1 Week 3. Drug: placebo Phase 3, Arm 2 placebo will be administered by intralesional injection at Day 1 Week 0, 3, 5, 7 then every 3 weeks starting at Day 1 Week 9. |
- Incidence of dose limiting toxicities (DLT) [ Time Frame: Start of treatment until 6 weeks from the initial administration of pembrolizumab (MK-3475) ]Phase 1b: To evaluate the safety, as assessed by incidence of dose limiting toxicity (DLT), of talimogene laherparepvec in combination with pembrolizumab (MK-3475)
- Progression Free Survival (PFS) (response evaluation by blinded central review assessed modified RECIST 1.1) [ Time Frame: up to 44 months ]Phase 3: 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 1.1 [RECIST]).
- Overall Survival [ Time Frame: up to 62 months ]Phase 3: To evaluate the efficacy of talimogene laherparepvec with pembrolizumab versus placebo with pembrolizumab, as assessed by overall survival (OS).
- Incidence of adverse events (AEs) [ Time Frame: Start of treatment to 30 (+7) days after end of treatment ]Incidence of treatment-emergent and treatment-related adverse events and abnormal laboratory tests (all AEs, grade ≥ 3 AEs, serious adverse events, fatal AEs, and AEs defined as events of interest)
- Objective Response Rate (ORR) [ Time Frame: Start of treatment and every 12 weeks until confirmed disease progression, assessed up to 60 months ]To evaluate the efficacy, as assessed by ORR of treatment with talimogene laherparepvec in combination with pembrolizumab in Phase 1b and talimogene laherparepvec in combination with pembrolizumab verses placebo in Phase 3.
- Best overall response (BOR) [ Time Frame: Start of treatment and every 12 weeks until confirmed disease progression, assessed up to 60 months ]To be assessed for Phase 3
- Durable response rate (DRR) defined as rate of objective responses for a duration of 6 months or longer [ Time Frame: Start of treatment and every 12 weeks until confirmed disease progression, assessed up to 60 months ]To be assessed for Phase 1b, Phase 3
- Duration of response (DOR) [ Time Frame: Start of treatment and every 12 weeks until confirmed disease progression, assessed up to 60 months ]To be assessed for Phase 1b, Phase 3
- Disease Control Rate (DCR) [ Time Frame: Start of treatment and every 12 weeks until confirmed disease progression, assessed up to 60 months ]To be assessed for Phase 1b, Phase 3
- Overall survival (OS) [ Time Frame: Start of treatment and every 12 weeks during long term follow up until 60 months after last subject enrolled. Calculated from date of Randomization to date of death. ]To be assessed for Phase 1b, Phase 3
- As assessed by the QLQ-C30 subject questionnaires [ Time Frame: weeks 0, then every 3, 6, 9, 12 weeks then every 6 weeks until the end of the study and at safety follow up, assessed up to 60 months ]Phase 3: To evaluate patient reported outcomes (PRO)
- Complete response rate (CRR) [ Time Frame: Start of treatment and every 12 weeks until confirmed disease progression, assessed up to 60 months ]by blinded independent central assessed modified immune-related response criteria simulating response evaluation criteria in solid tumors for Phase 3

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Ages Eligible for Study: | 18 Years to 95 Years (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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.
- ECOG performance status of 0 or 1.
- Adequate hematologic, hepatic, renal, and coagulation function.
- Subjects with 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 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.

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02263508

Study Director: | MD | Amgen |
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | Amgen |
ClinicalTrials.gov Identifier: | NCT02263508 |
Other Study ID Numbers: |
20110265 2014-000185-22 ( EudraCT Number ) KEYNOTE-034 ( Other Identifier: Merck Sharp & Dohme Corp. ) |
First Posted: | October 13, 2014 Key Record Dates |
Last Update Posted: | December 22, 2020 |
Last Verified: | December 2020 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | Yes |
Plan Description: | De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request |
Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Informed Consent Form (ICF) Clinical Study Report (CSR) |
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. |
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. |
URL: | https://www.amgen.com/datasharing |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
Talimogene Laherparepvec pembrolizumab KEYNOTE-034 MASTERKEY-265 |
Melanoma Neuroendocrine Tumors Neuroectodermal Tumors Neoplasms, Germ Cell and Embryonal Neoplasms by Histologic Type Neoplasms |
Neoplasms, Nerve Tissue Nevi and Melanomas Pembrolizumab Talimogene laherparepvec Antineoplastic Agents, Immunological Antineoplastic Agents |