MK 3475 With or Without Talimogene Laherparepvec in Unresected Melanoma

Phase 1

• Conditions: Previously Untreated, Unresected, Stage IIIB to IVM1c Melanoma; MedDRA version: 17.0Level: LLTClassification code 10053571Term: MelanomaSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-000185-22-ES
• Lead Sponsor: Amgen Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-08-06
• Last Update Posted: 19 April 2021

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 110

Inclusion Criteria

Phase 1b and Part 1 of Phase 2:
Male or female age ? 18 years with histologically confirmed diagnosis of melanoma and stage IIIB to IVM1c for whom surgery in not recommended. Subject must be treatment naïve (ie, must not
have received any prior systemic anticancer treatment consisting of chemotherapy, immunotherapy, or targeted therapy for unresected stage IIIB to IVM1c melanoma. Subject who received prior adjuvant therapy for melanoma will not be excluded (including, but not limited to, interferon, limb infusion/perfusion, or use of investigational agents in the adjuvant setting). However, if the subject received adjuvant therapy, the subject must have completed therapy at
least 6 months prior to enrollment. Subject must have measurable disease and be a candidate for intralesional therapy administration into cutaneous, subcutaneous, or nodal lesions. Subject must have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, and adequate hematologic, hepatic, renal, and coagulation function.

Part 2 of Phase 2:
Subject randomized to arm 2 (MK-3475 monotherapy arm) of part 1 of the phase 2 study must have evidence of PD at week 12 or subsequent tumor assessment visit through month 20
documented by an independent central review committee and confirmed by the investigator ? 4 weeks later using modified irRC. Subject must have ECOG performance status of 0 or 1, and
adequate hematologic, hepatic, renal, and coagulation function
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 57
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 53

Exclusion Criteria

Phase 1b and Part 1 of Phase 2:
Subject must not have clinically active cerebral metastases. Subject with up to 3 cerebral metastases, and neurological performance status of 0 may be enrolled, provided that all lesions have been adequately treated with stereotactic radiation therapy, craniotomy, or gammaknife therapy, with no evidence of progression, and have not required steroids, for at least 2 months prior to enrollment. Subject must not have primary uveal or mucosal melanoma, history or evidence of melanoma associated with immunodeficiency states (eg, hereditary immune deficiency, organ transplant, or leukemia), or history of other malignancy within the past 3 years with the exceptions of the prior malignancies. Subject must not have received prior talimogene laherparepvec, tumor vaccine, MK-3475, other anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, ipilimumab, other cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) inhibitor, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways, even if given in the adjuvant setting. Subject 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 steroids or immunosuppressive agents (except vitiligo or resolved childhood asthma/atopy), or evidence of clinically significant immunosuppression. Subject 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.

Part 2 of Phase 2:
Subject must not have stopped MK-3475 treatment in part 1 of phase 2 due to intolerance or reasons other than confirmed PD per modified irRC at week 12 or subsequent tumor assessment visit through month 20. Subject 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 steroids or immunosuppressive agents (except vitiligo or resolved
childhood asthma/atopy), or evidence of clinically significant immunosuppression. Subject 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