Talimogene Laherparepvec With Pembrolizumab in Melanoma Following Progression on Prior Anti-PD-1 Based Therapy (MASTERKEY-115) (Mk-3475-A07/KEYNOTE-A07).
Condition: Melanoma
MeSH terms: Melanoma
Intervention: Talimogene laherparepvec; Pembrolizumab
Intervention description: Intralesional injection into injectable cutaneous, subcutaneous and nodal legions.; Intravenous (IV) infusion.
Intervention MeSH terms: Pembrolizumab; Talimogene laherparepvec
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 72.0
Sex: All
Minimum age: 18 Years
Maximum age: 99 Years
Healthy volunteers: No
Keywords: Melanoma; Talimogene Laherparepvec; Pembrolizumab; Oncolytic immunotherapy; Anti-PD-1; Checkpoint inhibitor; MASTERKEY-115

Summary:

      This is a phase 2, open-label, single-arm, multicenter clinical trial designed to evaluate
      the efficacy and safety of talimogene laherparepvec in combination with pembrolizumab
      following disease progression on prior anti-programmed cell death protein (anti-PD-1) therapy
      in unresectable/metastatic melanoma (stage IIIB-IVM1d) or prior anti-PD-1 therapy in the
      adjuvant setting. Subjects will be treated with talimogene laherparepvec and pembrolizumab
      until confirmed complete response, disappearance of all injectable lesions, documented
      confirmed disease progression per modified immune-related Response Criteria simulating
      Response Evaluation Criteria in Solid Tumors (irRC-RECIST), intolerance of study treatment,
      or 102 weeks from the first dose of talimogene laherparepvec and/or pembrolizumab, whichever
      occurs first.
    

Eligibility criteria:

        Key Inclusion Criteria:

          -  Age ≥ 18 years with histologically confirmed diagnosis of stage IIIB to IVM1d melanoma
             and for whom surgery is not recommended. Subjects with stage IVM1d disease may be
             enrolled with up to 3 cerebral metastases, provided that all lesions have been
             adequately treated with stereotactic radiation therapy, craniotomy, or gamma knife
             therapy, with no evidence of progression and not requiring steroids for at least 2
             months prior to enrollment.

          -  Subjects must have measurable disease and be a candidate for intralesional therapy
             administration into cutaneous, subcutaneous, or nodal lesions.

          -  Subjects must have had prior treatment (for at least 2 to 3 consecutive cycles within
             an 8 week period) with a PD-1 inhibitor and have confirmed disease progression (as
             defined by RECIST v1.1 criteria). The anti-PD-1 therapy must be the immediate prior
             line of therapy before enrollment and subjects with disease progression on more than 1
             line of anti-PD-1 therapy are not eligible.

          -  ECOG performance status of 0 or 1.

          -  Adequate hematologic, renal, hepatic, and coagulation function.

        Key Exclusion Criteria:

          -  Subjects considered by the investigator to have rapid clinical progression due to
             melanoma

          -  Subjects with prior treatment and disease progression on more than 1 line of anti-PD-1
             therapy

          -  Stage IVM1d subjects must not have greater than 3 cerebral melanoma metastases, or
             clinically active cerebral melanoma metastases requiring therapy, and/or carcinomatous
             meningitis regardless of clinical stability.

          -  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 must not have history or evidence of symptomatic autoimmune
             glomerulonephritis, vasculitis, or other symptomatic autoimmune disease, or active
             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 may not have been previously treated with talimogene laherparepvec or any
             other oncolytic virus.

          -  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.