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

Trial details

Who runs it

Pfizer Inc.

Trial code

EU 2023-509471-17-00

Record updated

2025. november 12.

Original description

To compare the efficacy of encorafenib and binimetinib plus pembrolizumab (Triplet Arm) versus nivolumab and ipilimumab (Control Arm) with respect to ORR.Read full original descriptionShow less

C4221023 - A PHASE 2, RANDOMIZED, OPEN-LABEL STUDY OF ENCORAFENIB AND BINIMETINIB PLUS PEMBROLIZUMAB VERSUS NIVOLUMAB AND IPILIMUMAB IN PARTICIPANTS WITH BRAF V600E/K MUTATION-POSITIVE MELANOMA WHO PROGRESSED DURING OR AFTER PRIOR TREATMENT WITH ANTI−PD-1 THERAPY

To compare the efficacy of encorafenib and binimetinib plus pembrolizumab (Triplet Arm) versus nivolumab and ipilimumab (Control Arm) with respect to ORR.

Inclusion: 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: 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; History of thromboembolic or cerebrovascular events ≤12 weeks prior to randomization; 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; Prior or current symptomatic brain metastasis, leptomeningeal disease or other active CNS metastases; Clinically significant cardiovascular diseases; Current noninfectious pneumonitis/ILD or history of noninfectious pneumonitis/ILD requiring steroids; Mucosal or ocular melanoma; History or current evidence of RVO or current risk factors for RVO.

EU CTIS 2023-509471-17-00