Phase 2 Study of Encorafenib and Binimetinib Plus Pembrolizumab in Participants With BRAF V600E/K Mutation-Positive Melanoma Who Progressed During or After Prior Treatment with Anti-PD-1 Therapy

Phase 1

• Conditions: Metastatic or unresectable locally advanced BRAF V600E/K mutation positive melanoma; MedDRA version: 21.1Level: LLTClassification code: 10053571Term: Melanoma Class: 10029104; MedDRA version: 20.0Level: PTClassification code: 10077160Term: Central nervous system melanoma Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code: 10025663Term: Malignant melanoma of skin of trunk except scrotum Class: 10029104; MedDRA version: 21.1Level: PTClassification code: 10027480Term: Metastatic malignant melanoma Class: 100000004864; MedDRA version: 21.1Level: PTClassification code: 10025671Term: Malignant melanoma stage IV Class: 100000004864; MedDRA version: 21.1Level: LLTClassification code: 10025660Term: Malignant melanoma of skin of lower limb including hip Class: 10029104; MedDRA version: 21.1Level: LLTClassification code: 10056768Term: Malignant melanoma of skin of lower limb incl hip Class: 10029104; MedDRA version: 21.1Level: LLTClassification code: 10056767Term: Malignant melanoma of skin of eyelid incl canthus Class: 10029104; MedDRA version: 20.0Level: HLTClassification code: 10027156Term: Skin melanomas (excl ocular) Class: 10040785

• Registration Number: CTIS2023-509471-17-00
• Lead Sponsor: Pfizer Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-05-21
• Last Update Posted: 21 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 141

Inclusion Criteria

Male or female participants =18 years of age at the time of informed consent., Histologically confirmed unresectable (Stage IIIB, IIIC, or IIID) or metastatic (Stage IV) cutaneous melanoma, according to the AJCC 8th edition., Documented evidence of a BRAF V600E or V600K mutation., Availability of adequate tumor tissue for central laboratory testing of biomarkers is required for all participants during the screening period., Must have received only 1 prior line of systemic therapy for melanoma (either adjuvant therapy or first-line anti-PD-1 monotherapy (ie, nivolumab or pembrolizumab)., Must have anti-PD-1 resistant disease (primary or secondary) with confirmed disease progression per RECIST v1.1 either during or after receipt of an approved anti-PD-1 monotherapy (ie, nivolumab or pembrolizumab) for melanoma, defined according to the SITC Immunotherapy Resistance Taskforce (Kluger et al, 2020)., Have at least 1 measurable lesion per RECIST v1.1., ECOG PS of 0-1, and adequate organ and cardiac function, including LVEF =50% by cardiac imaging.

Exclusion Criteria

Mucosal or ocular melanoma., Participants who permanently discontinued prior anti-PD-1 therapy due to toxicity or will be unable to tolerate combination therapy based on investigator judgement are excluded., Prior treatment with ipilimumab; prior combined immunotherapy blockade with anti- PD-1/L-1; prior treatment with a BRAFi and/or MEKi; or previous administration of an investigational anticancer agent for the adjuvant or first-line treatment of melanoma prior to randomization., Previous participation in the Pfizer C4221016 STARBOARD Study., Diagnosis of immunodeficiency or an active autoimmune disease that required systemic treatment with chronic systemic steroid therapy or any other form of immunosuppressive therapy within the past 2 years., Clinically significant cardiovascular diseases., History of thromboembolic or cerebrovascular events =12 weeks prior to randomization., History or current evidence of RVO or current risk factors for RVO., Concurrent neuromuscular disorder that is associated with the potential of elevated CK., Active bacterial, fungal, or viral infection requiring systemic therapeutic treatment within 2 weeks prior to randomization., Current noninfectious pneumonitis/ILD or history of noninfectious pneumonitis/ILD requiring steroids., Prior or current symptomatic brain metastasis, leptomeningeal disease or other active CNS metastases.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To compare the efficacy of encorafenib and binimetinib plus pembrolizumab (Triplet Arm) versus nivolumab and ipilimumab (Control Arm) with respect to ORR.;Secondary Objective: To compare the efficacy of the Triplet Arm versus the Control Arm with respect to PFS., To compare the efficacy of the Triplet Arm versus the Control Arm with respect to OS.;Primary end point(s): ORR, defined as the proportion of participants with a confirmed best overall response of either CR or PR, as determined by investigator assessment per RECIST v1.1 from randomization to the earliest of PD, start of subsequent anticancer therapy, or death due to any cause.