Study

Overview

Official Title: A Phase 1/2 Open-Label Rolling-Arm Umbrella Platform Design of Investigational Agents With or Without Pembrolizumab or Pembrolizumab Alone in Participants with Melanoma (KEYMAKER-U02): Substudy 02C

Substudy 02C is part of a larger research study that is testing experimental treatments for melanoma, a type of skin cancer. The larger study is the umbrella study. The goal of substudy 02C is to evaluate the safety and efficacy of investigational treatment arms in participants with Stage III melanoma who are candidates for neoadjuvant therapy to identify the investigational agent(s) that, when used in combination, are superior to the current treatment options/historical control available. Arm 1: Pembrolizumab + Vibostolimab, Arm 2: Pembrolizumab + Gebasaxturev, and Arm 3: Pembrolizumab were added in the base protocol on 13-Nov-2019, and enrollment into those arms has been completed. Arm 4: Pembrolizumab + MK-4830 was added in Amendment 04 on 20-Dec-2021, and enrollment into that arm has been completed. Arm 5: Favezelimab + Pembrolizumab and Arm 6: Pembrolizumab + all-trans retinoic acid (ATRA) were added in Amendment 06 on 25-Jun-2022, and enrollment is ongoing.

Study Type:

Interventional

Study Phase:

Phase 1/Phase 2

Estimated Enrollment:

90

Study Start Date:

June 2020

Estimated Study Completion Date:

April 2030

Estimated Primary Completion Date:

April 2030

Eligibility

Ages Eligible for Study:

18 years to 120 years

Genders Eligible for Study:

All

Accepts Healthy Volunteers:

No

CRITERIA

Inclusion Criteria:

Has histologically or cytologically confirmed melanoma
Has clinically detectable and resectable Stage IIIB or IIIC or IIID melanoma amenable to surgery
Has been untreated for Stage IIIB, IIIC or IIID melanoma
- surgical resection of primary melanoma is allowed
- prior radiotherapy to the primary melanoma is allowed
Has provided a baseline tumor biopsy
Male participants who receive gebasaxturev are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 120 days after the last dose of gebasaxturev
Male participants who receive ATRA are abstinent from heterosexual intercourse or agree to use contraception during the intervention period and for at least 7 days after the last dose of ATRA
Female participants are not pregnant or breastfeeding and are either not a woman of child-bearing potential (WOCBP) OR use a contraceptive method that is highly effective or are abstinent from heterosexual intercourse during the intervention period and for at least 120 days after the last dose of pembrolizumab, vibostolimab, gebasaxturev, or MK-4830, favezelimab + pembrolizumab, or 30 days after the last dose of ATRA, whichever occurs last
Has adequate organ function
Has resolution of toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia)

Exclusion Criteria:

Has a diagnosis of immunodeficiency or is receiving immunosuppressive therapy within 7 days before the first dose of study intervention
Has a known additional malignancy that is progressing or requires active treatment within the past 2 years
Has known central nervous system (CNS) metastases and/or carcinomatous meningitis
Has ocular or mucosal melanoma
Has known hypersensitivity including previous clinically significant hypersensitivity reaction to treatment with another monoclonal antibody (mAb)
Has an active autoimmune disease that has required systemic treatment in the past 2 years
Has an active infection requiring systemic therapy
Has known history of human immunodeficiency virus (HIV)
Has known history of hepatitis B
Has a history of (noninfectious) pneumonitis
Has a history of active tuberculosis (TB)
Has received prior systemic anticancer therapy within 4 weeks prior to randomization
Has received prior radiotherapy within 2 weeks of first dose of study intervention
Has had major surgery <3 weeks prior to first dose of study intervention
Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention
Has participated in a study of an investigational agent within 4 weeks prior to the first dose of study intervention
Has had an allogeneic tissue/solid organ transplant
Has only mucosal lesions
Is not naïve to Talimogene laherparepvec (TVEC) and other oncolytic viruses

Study Detail

Substudy 02C: Safety and Efficacy of Pembrolizumab in Combination with Investigational Agents or Pembrolizumab Alone in Participants With Stage III Melanoma Who Are Candidates for Neoadjuvant Therapy (MK-3475-02C/KEYMAKER-U02)

Overview

Eligibility

CRITERIA

Locations

Results

Plain Language Summaries