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Pembrolizumab With or Without Talimogene Laherparepvec or Talimogene Laherparepvec Placebo in Unresected Melanoma (KEYNOTE-034)

This study is currently recruiting participants.
Verified November 2017 by Amgen
Sponsor:
ClinicalTrials.gov Identifier:
NCT02263508
First Posted: October 13, 2014
Last Update Posted: November 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Amgen
  Purpose
Phase 1b Subjects will be treated with talimogene laherparepvec until all injectable tumors have disappeared, disease progression per modified Immune-Related Response Criteria (irRC), or intolerance of study treatment, up to a maximum of 24 months of study treatment. Subjects will be treated with MK-3475 (pembrolizumab) until complete response (CR) disease progression per irRC, or intolerance of study treatment, up to a maximum of 24 months of study treatment. In Phase 3, Subjects will be treated with talimogene laherparepvec plus pembrolizumab(arm 1) or placebo plus pembrolizumab (arm 2) until 24 months from the date of the first dose of pembrolizumab or end of treatment due to disappearance of injectable lesions, complete response, disease progression per irRC-RECIST or intolerance of study treatment.

Condition Intervention Phase
Melanoma Drug: talimogene laherparepvec Drug: pembrolizumab (MK-3475) Drug: placebo Phase 3

Study Type: Interventional
Study Design: 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)

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • 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).


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 660
Actual Study Start Date: December 8, 2014
Estimated Study Completion Date: September 14, 2022
Estimated Primary Completion Date: December 31, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1b;
Phase 1b: 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 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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 95 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  • 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.
  Contacts and Locations
Information from the National Library of Medicine

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


Contacts
Contact: Amgen Call Center 866-572-6436 medinfo@amgen.com

  Show 158 Study Locations
Sponsors and Collaborators
Amgen
Merck Sharp & Dohme Corp.
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
Publications:
Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02263508     History of Changes
Other Study ID Numbers: 20110265
2014-000185-22 ( EudraCT Number )
KEYNOTE-034 ( Other Identifier: Merck Sharp & Dohme Corp. )
First Submitted: September 26, 2014
First Posted: October 13, 2014
Last Update Posted: November 6, 2017
Last Verified: November 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Amgen:
Talimogene Laherparepvec
pembrolizumab
KEYNOTE-034
MASTERKEY-265

Additional relevant MeSH terms:
Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Pembrolizumab
Antineoplastic Agents