Safety and Efficacy in Participants With Metastatic BRAF-mutant Melanoma Treated With Encorafenib With and Without Binimetinib in Combination With Nivolumab and Low-dose Ipilimuma

Part of paid clinical trials in Pittsburgh, Pennsylvania.

Sponsor
Jason J. Luke, MD
Study ID
NCT04655157
Phase
PHASE1/PHASE2
Status
Terminated

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • encorafenib — DRUG
    A small molecule BRAF inhibitor that targets key enzymes in the MAPK signaling pathway.
  • nivolumab — DRUG
    A programmed death receptor-1 (PD-1) blocking monoclonal antibody that works by helping the immune system to slow or stop the growth of cancer cells.
  • ipilimumab — DRUG
    A monoclonal antibody medication that works to activate the immune system by targeting CTLA-4, a protein receptor that downregulates the immune system.
  • binimetinib — DRUG
    A small molecule, selective inhibitor of MEK, a central kinase in the tumor-promoting MAPK pathway that may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Study Details

Patients with unresectable or metastatic BRAF-mutant melanoma high-risk patients will be given 450 mg orally (PO) daily (QD) plus binimetinib 45 mg PO twice daily (BID) together with nivolumab administered intravenously (IV) at 3mg/kg and ipilimumab administered IV at 1 mg/kg every 3 weeks for 4 doses, followed by nivolumab administered IV at 480mg every 4 weeks until progression or discontinuation due to toxicity. Concurrently, a triple therapy arm will be explored with encorafenib 300 mg PO QD together with ipilimumab administered IV at 1mg/kg and nivolumab 3mg/kg IV every 3 weeks for 4 doses, followed by nivolumab administered at 480mg every 4 weeks until progression or discontinuation due to toxicity. Tolerability of the two arms will be compared, and a recommended phase 2 dose (RP2D) will be determined. After determination of treatment schedule, expansion cohorts will further explore the preliminary efficacy and further describe the toxicity profile of the triplet or quadruplet regimen in high-risk cohorts including symptomatic brain metastases or liver metastases with elevated lactate dehydrogenase (LDH) or bulky systemic disease burden.

Key Dates

Start date
May 28, 2021
Status verified
Apr 2024
Primary completion
Aug 3, 2022
Completion
Sep 20, 2022

Study Design

Enrollment
2 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Phase 1 (cohort 1): 300mg encorafenib + 3mg/kg nivolumab + 1 mg/kg ipilimumab
    Patients will be treated with 300mg encorafenib and 3mg/kg nivolumab and 1 mg/kg ipilimumab (triple therapy).
  • Experimental: Phase 1 (cohort 2): 450mg encorafenib + 45mg binimetinib + 3mg/kg nivolumab + 1mg/kg ipilimumab
    Patients will be treated with 450mg encorafenib, 45mg binimetinib, 3mg/kg nivolumab and 1mg/kg ipilimumab (quadruple therapy).

Primary Outcome Measure

Recommended Phase II Dose (RP2D) of Encorafenib + Nivolumab + Ipilimumab [ Time Frame: Up to 6 weeks (DLT evaluation period) ]

Locations (1)

FacilityCityStateZIPSite coordinators
UPMC Hillman Cancer CenterPittsburghPennsylvania15232-

Find similar trials in Pittsburgh, PA

By condition
Melanoma
By specialty
OncologySkin cancerDermatology
By research site
UPMC Hillman Cancer Center· Pittsburgh, PA

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