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

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. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02263508
Recruitment Status : Active, not recruiting
First Posted : October 13, 2014
Last Update Posted : December 19, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Amgen

Brief Summary:
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 or disease Intervention/treatment Phase
Melanoma Drug: talimogene laherparepvec Drug: pembrolizumab (MK-3475) Drug: placebo Phase 3

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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)
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.




Primary Outcome Measures :
  1. 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)

  2. 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]).

  3. 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 :
  1. 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)

  2. 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.

  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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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)

  9. 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



Information from the National Library of Medicine

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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
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.

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


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Locations
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United States, Alabama
Research Site
Birmingham, Alabama, United States, 35243
Research Site
Mobile, Alabama, United States, 36608
United States, California
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Beverly Hills, California, United States, 90211
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Duarte, California, United States, 91010
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Encinitas, California, United States, 92024
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La Jolla, California, United States, 92037
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Los Angeles, California, United States, 90024
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Los Angeles, California, United States, 90025
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Riverside, California, United States, 92505
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San Francisco, California, United States, 94115
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San Francisco, California, United States, 94117
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Santa Monica, California, United States, 90404
United States, Florida
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Miami Beach, Florida, United States, 33140
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Miami, Florida, United States, 33136
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Orlando, Florida, United States, 32806
United States, Georgia
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Atlanta, Georgia, United States, 30322
United States, Illinois
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Chicago, Illinois, United States, 60611
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Chicago, Illinois, United States, 60637
United States, Kentucky
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Louisville, Kentucky, United States, 40202
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Baltimore, Maryland, United States, 21237
United States, Massachusetts
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Boston, Massachusetts, United States, 02215
United States, Michigan
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Detroit, Michigan, United States, 48201
United States, Minnesota
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Fridley, Minnesota, United States, 55432
United States, Missouri
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Saint Louis, Missouri, United States, 63110-1093
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Hackensack, New Jersey, United States, 07601
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Buffalo, New York, United States, 14263
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New York, New York, United States, 10016
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New York, New York, United States, 10032
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New York, New York, United States, 10065
United States, Ohio
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Cincinnati, Ohio, United States, 45209
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Cleveland, Ohio, United States, 44195
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Philadelphia, Pennsylvania, United States, 19107
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Philadelphia, Pennsylvania, United States, 19111
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Pittsburgh, Pennsylvania, United States, 15232
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Germantown, Tennessee, United States, 38138
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Knoxville, Tennessee, United States, 37920
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Nashville, Tennessee, United States, 37232
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Dallas, Texas, United States, 75246
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Murray, Utah, United States, 84107
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Salt Lake City, Utah, United States, 84112
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Seattle, Washington, United States, 98109-1023
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North Sydney, New South Wales, Australia, 2060
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Waratah, New South Wales, Australia, 2298
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Wollongong, New South Wales, Australia, 2500
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Southport, Queensland, Australia, 4215
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Woolloongabba, Queensland, Australia, 4102
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Woodville South, South Australia, Australia, 5011
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Geelong, Victoria, Australia, 3220
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Heidelberg, Victoria, Australia, 3084
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Melbourne, Victoria, Australia, 3000
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Prahran, Victoria, Australia, 3181
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Murdoch, Western Australia, Australia, 6150
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Graz, Austria, 8036
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Innsbruck, Austria, 6020
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Wien, Austria, 1090
Belgium
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Bruxelles, Belgium, 1200
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Liege, Belgium, 4000
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Edmonton, Alberta, Canada, T6G 1Z2
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Kingston, Ontario, Canada, K7L 2V7
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Montreal, Quebec, Canada, H3T 1E2
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Brno, Czechia, 656 53
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Olomouc, Czechia, 775 20
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Praha 10, Czechia, 100 34
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Praha 2, Czechia, 128 08
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Praha 8, Czechia, 180 81
Finland
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Helsinki, Finland, 00290
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Bordeaux Cedex, France, 33075
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Lille, France, 59037
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Lyon cedex 08, France, 69373
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Pierre Benite Cedex, France, 69495
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Vandoeuvre les Nancy, France, 54511
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Berlin, Germany, 10117
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Dresden, Germany, 01307
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Erlangen, Germany, 91054
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Essen, Germany, 45147
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Hannover, Germany, 30625
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Heidelberg, Germany, 69120
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Kiel, Germany, 24105
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Mainz, Germany, 55131
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Mannheim, Germany, 68167
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München, Germany, 80337
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Regensburg, Germany, 93053
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Tübingen, Germany, 72076
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Würzburg, Germany, 97080
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Athens, Greece, 11527
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Athens, Greece, 18547
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Heraklion - Crete, Greece, 71110
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Ioannina, Greece, 45500
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Thessaloniki, Greece, 54622
Hungary
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Budapest, Hungary, 1122
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Szeged, Hungary, 6720
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Bergamo, Italy, 24127
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Meldola FC, Italy, 47014
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Milano, Italy, 20133
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Milano, Italy, 20141
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Siena, Italy, 53100
Korea, Republic of
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Seoul, Korea, Republic of, 03722
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Seoul, Korea, Republic of, 05505
Netherlands
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Amsterdam, Netherlands, 1066 CX
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Amsterdam, Netherlands, 1081 HV
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Groningen, Netherlands, 9713 GZ
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Nijmegen, Netherlands, 6525 GA
Poland
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Bielsko-Biala, Poland, 43-300
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Bydgoszcz, Poland, 85-796
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Gdansk, Poland, 80-952
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Konin, Poland, 62-500
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Wroclaw, Poland, 50-368
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Almada, Portugal, 2801-951
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Lisboa, Portugal, 1099-023
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Lisboa, Portugal, 1649-035
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Porto, Portugal, 4200-072
Russian Federation
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Moscow, Russian Federation, 115478
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Saint-Petersburg, Russian Federation, 197758
South Africa
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Groenkloof, Gauteng, South Africa, 0181
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Johannesburg, Gauteng, South Africa, 2196
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Parktown, Gauteng, South Africa, 2193
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Kraaifontein, South Africa, 7570
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Pretoria, South Africa, 0002
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Pretoria, South Africa, 0081
Spain
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Badalona, Cataluña, Spain, 08916
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Barcelona, Cataluña, Spain, 08036
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Valencia, Comunidad Valenciana, Spain, 46014
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Pamplona, Navarra, Spain, 31008
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San Sebastian, País Vasco, Spain, 20014
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Madrid, Spain, 28009
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Madrid, Spain, 28046
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Madrid, Spain, 28050
Switzerland
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Bellinzona, Switzerland, 6500
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Bern, Switzerland, 3010
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Geneva 14, Switzerland, 1211
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Lausanne, Switzerland, 1011
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Zürich, Switzerland, 8091
United Kingdom
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Birmingham, United Kingdom, B15 2TH
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Guildford, United Kingdom, GU2 7XX
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Leeds, United Kingdom, LS9 7TF
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Leicester, United Kingdom, LE1 5WW
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London, United Kingdom, SE1 9RT
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London, United Kingdom, SW3 6JJ
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Manchester, United Kingdom, M20 4BX
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Oxford, United Kingdom, OX3 7LJ
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Preston, United Kingdom, PR2 9HT
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Southampton, United Kingdom, SO16 6YD
Sponsors and Collaborators
Amgen
Merck Sharp & Dohme Corp.
Investigators
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Study Director: MD Amgen

Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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 Posted: October 13, 2014    Key Record Dates
Last Update Posted: December 19, 2018
Last Verified: December 2018
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

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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:
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Melanoma
Nevi and Melanomas
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Pembrolizumab
Talimogene laherparepvec
Antineoplastic Agents, Immunological
Antineoplastic Agents