Clinical Trials /

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

NCT02263508

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Active, not recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Pembrolizumab With or Without Talimogene Laherparepvec or Talimogene Laherparepvec Placebo in Unresected Melanoma (KEYNOTE-034)
  • 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)

Clinical Trial IDs

  • ORG STUDY ID: 20110265
  • SECONDARY ID: 2014-000185-22
  • SECONDARY ID: KEYNOTE-034
  • NCT ID: NCT02263508

Conditions

  • Melanoma

Interventions

DrugSynonymsArms
talimogene laherparepvecPhase 1b;
pembrolizumab (MK-3475)Phase 1b;
placeboPhase 3 Arm 2;

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.

Trial Arms

NameTypeDescriptionInterventions
Phase 1b;ExperimentalPhase 1b: talimogene laherparepvec and pembrolizumab (MK-3475)
  • talimogene laherparepvec
  • pembrolizumab (MK-3475)
Phase 3 Arm 1;ExperimentalPhase 3 Arm 1: talimogene laherparepvec and pembrolizumab (MK-3475)
  • talimogene laherparepvec
  • pembrolizumab (MK-3475)
Phase 3 Arm 2;ExperimentalPhase 3 Arm 2: placebo and pembrolizumab (MK-3475)
  • pembrolizumab (MK-3475)
  • placebo

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.

          -  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.
      
Maximum Eligible Age:95 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of dose limiting toxicities (DLT)
Time Frame:Start of treatment until 6 weeks from the initial administration of pembrolizumab (MK-3475)
Safety Issue:
Description:Phase 1b: To evaluate the safety, as assessed by incidence of dose limiting toxicity (DLT), of talimogene laherparepvec in combination with pembrolizumab (MK-3475)

Secondary Outcome Measures

Measure:Incidence of adverse events (AEs)
Time Frame:Start of treatment to 30 (+7) days after end of treatment
Safety Issue:
Description: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)
Measure:Objective Response Rate (ORR)
Time Frame:Start of treatment and every 12 weeks until confirmed disease progression, assessed up to 60 months
Safety Issue:
Description: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.
Measure:Best overall response (BOR)
Time Frame:Start of treatment and every 12 weeks until confirmed disease progression, assessed up to 60 months
Safety Issue:
Description:To be assessed for Phase 3
Measure: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
Safety Issue:
Description:To be assessed for Phase 1b, Phase 3
Measure:Duration of response (DOR)
Time Frame:Start of treatment and every 12 weeks until confirmed disease progression, assessed up to 60 months
Safety Issue:
Description:To be assessed for Phase 1b, Phase 3
Measure:Disease Control Rate (DCR)
Time Frame:Start of treatment and every 12 weeks until confirmed disease progression, assessed up to 60 months
Safety Issue:
Description:To be assessed for Phase 1b, Phase 3
Measure: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.
Safety Issue:
Description:To be assessed for Phase 1b, Phase 3
Measure: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
Safety Issue:
Description:Phase 3: To evaluate patient reported outcomes (PRO)
Measure:Complete response rate (CRR)
Time Frame:Start of treatment and every 12 weeks until confirmed disease progression, assessed up to 60 months
Safety Issue:
Description:by blinded independent central assessed modified immune-related response criteria simulating response evaluation criteria in solid tumors for Phase 3

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Amgen

Trial Keywords

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

Last Updated

September 13, 2017