Pembrolizumab With Talimogene Laherparepvec or Placebo in Unresected Melanoma
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Talimogene Laherparepvec; Pembrolizumab; Placebo
Intervention description: Talimogene laherparepvec administered by intratumoral injection; Administered at a dose of 200 mg as an intravenous infusion over approximately 30 minutes.; Administered by intratumoral injection
Intervention MeSH terms: Pembrolizumab; Talimogene laherparepvec
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Phase 1b was an open-label, single-arm study. Phase 3 was a randomized, double-blind, placebo-controlled study design.
Masking: Double (Participant, Investigator)
Enrollment: 713.0
Sex: All
Minimum age: 18 Years
Maximum age: 95 Years
Healthy volunteers: No
Keywords: Talimogene Laherparepvec; pembrolizumab; KEYNOTE-034; MASTERKEY-265

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).
    

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.