Pembrolizumab (MK 3475) With Talimogene Laherparepvec or placebo in Unresectable Melanoma

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 680

Inclusion Criteria

Phase 1b and Phase 3:
• Male or female age = 18 years with histologically confirmed diagnosis of melanoma and stage IIIB to IVM1c for whom surgery in not recommended.
• Subjects must have measurable disease and be a candidate for intralesional therapy administration into cutaneous, subcutaneous, or nodal lesions.
• Subjects must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate hematologic, hepatic, renal, and coagulation function.

Phase 1b only:
• Subjects enrolled in phase 1b must be treatment naïve (i.e., 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 who received prior adjuvant therapy for melanoma will not be excluded (including, but not limited to, radiotherapy, interferon, 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 3 months prior to enrolment.

Phase 3 only:
• Subjects enrolled in phase 3 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 enrolled in phase 3 with 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 for the phase 3 of this study. Subjects with BRAFV600 mutant melanoma or unknown BRAFV600 mutation status who have not received a BRAF inhibitor are also eligible for the phase 3 of this study as first-line treatment if they meet the following criteria: lactate dehydrogenase (LDH) < upper limit of normal (ULN), no clinically significant tumor related symptoms, and absence of rapidly progressing metastatic melanoma. Subjects (BRAF mutant, wildtype and UNK) 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 PD-1 OR PD-L1 is not allowed. However, if the subject received adjuvant therapy, the subject must have completed therapy at least 28 days prior to enrolment.
• Subjects must have a tumor sample (archival sample or newly obtained biopsy) that is adequate for PD-L1 assessment prior to randomization.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 330
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 350

Exclusion Criteria

Phase 1b and Phase 3:
• Subjects must not have clinically active cerebral metastases and/or carcinomatous meningitis.
• Subjects with up to 3 cerebral metastases may be enrolled, 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 enrolment. Carcinomatous meningitis is excluded regardless of clinical stability.
• Subjects must not have primary uveal or mucosal melanoma, history or evidence of melanoma associated with immunodeficiency states (e.g., hereditary immune deficiency, organ transplant, or leukemia), or history of other malignancy within the past 3 years with the exceptions of the prior malignancies noted in Section 4.1.2.
• 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 programmed cell death ligand 2 (PD-L2). Prior treatment with other immunotherapies ( e.g., anti-CD137, or cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) inhibitor, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways), is allowed only in the adjuvant setting.
• Subjects must not have history or evidence of symptomatic autoimmune 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 (eg, herpetic keratitis or encephalitis) and must not require intermittent or chronic treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method

Secondary Outcome Measures

Name	Time	Method

Updated 4/19/2022

Pembrolizumab (MK 3475) With Talimogene Laherparepvec or placebo in Unresectable Melanoma

Recruitment & Eligibility

Study & Design

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