1091TiP - STARBOARD: Randomized phase III study of encorafenib (enco) + binimetinib (bini) + pembrolizumab (pembro) for first-line treatment of metastatic or unresectable locally advanced BRAF V600-mutant melanoma

Background

Approximately 50% of patients (pts) with metastatic melanoma have BRAF V600 mutations, which promote melanoma progression through constitutive activation of the MAPK pathway. Current treatment recommendations for metastatic or unresectable BRAF V600-mutant melanoma include BRAF inhibitors (BRAFi) + MEK inhibitors (MEKi) (eg, enco + bini) and immune checkpoint inhibitors (CPIs; eg, pembro). BRAFi and MEKi may increase the sensitivity of BRAF V600-mutant tumors to CPIs. STARBOARD aims to compare the efficacy, safety, and tolerability of first-line enco + bini + pembro vs pembro alone for the treatment of metastatic or unresectable locally advanced BRAF V600-mutant melanoma.

Trial design

STARBOARD is a randomized, double-blind, placebo-controlled, phase III study with a safety lead-in (SLI). Approximately 24 and 600 pts will be enrolled into the SLI and phase III study, respectively; phase III randomization will be stratified by prior systemic adjuvant treatment and disease stage. Pts must have histologically confirmed metastatic or unresectable cutaneous melanoma (AJCC 8th ed.) with BRAF V600E/K mutation (by local laboratory assay); measurable disease (RECIST v1.1); ECOG performance status 0 or 1; and adequate bone marrow, hepatic, and renal function. Pts must not have received prior first-line systemic therapy. Prior adjuvant treatment with BRAFi and/or MEKi or anti–PD-1 or anti–CTLA-4 is permitted. Pts with prior or current symptomatic brain metastases will be excluded except those with ≤ 3 brain lesions (either previously treated, asymptomatic, and stable for ≥ 28 days prior to enrolment; or untreated, asymptomatic, and each < 5 mm). Study treatments and endpoints are shown in the table. Enrolment began on 11 February 2021. Table: 1091TiP

AE, adverse event; DCR, disease control rate; DLT, dose-limiting toxicity; DOR, duration of response; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PFS2, PFS after next line of therapy; PK, pharmacokinetics; QOL, quality of life; TTR, time to response.

Clinical trial identification

NCT04657991.

Editorial acknowledgement

Editorial/medical writing support was provided by Jennifer Shepphird, PhD, at Caudex, and was funded by Pfizer.

Legal entity responsible for the study

The authors.

Funding

Array BioPharma, which was acquired by Pfizer in July 2019.

Disclosure

D. Schadendorf: Financial Interests, Personal, Advisory Board: 4SC; Financial Interests, Personal, Advisory Board: Array Biopharma; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Advisory Board: Immunocore; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: NEKTAR; Financial Interests, Personal, Advisory Board: Neracare; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Philogen; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Sandoz; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Advisory Board: Sanofi/Regeneron; Financial Interests, Personal, Member, Steering Committee Member: 4SC; Financial Interests, Institutional, Principal Investigator, Coordinating PI: 4SC; Financial Interests, Institutional, Research Grant: Array/Pfizer; Financial Interests, Institutional, Principal Investigator, Coordinating PI: BMS; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Personal, Member, Steering Committee Member: BMS; Financial Interests, Personal, Member, Steering Committee Member: MSD; Financial Interests, Institutional, Principal Investigator, Coordinating PI: MSD; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Personal, Member, Steering Committee Member: Nektar; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Nektar; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Personal, Member, Steering Committee Member: Novartis; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Novartis; Financial Interests, Institutional, Principal Investigator, Local PI: Philogen; Financial Interests, Institutional, Principal Investigator, Coordinating PI: Pierre Fabre; Financial Interests, Institutional, Principal Investigator, Local PI: Roche; Financial Interests, Institutional, Principal Investigator, Local PI: Sanofi; Financial Interests, Personal, Member, Member of Board of Directors: EORTC-MG. R. Dummer: Financial Interests, Personal, Advisory Board: Novartis, MSD, BMS, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, T3 Pharma, MaxiVAX SA, touchIME. C. Robert: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Pierre Fabre; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: AstraZeneca. A. Ribas: Financial Interests, Personal, Other, Honoraria for consulting: Amgen, Apexigen, AstraZeneca, Merck, Novartis, Sanofi, Vedanta; Financial Interests, Personal, Other, SAB member, honoraria, stock: Advaxis, Apricity, Arcus, Compugen, CytomX, Five Prime, Highlight, ImaginAb, Isoplexis, Kalthera, Kite-Gilead, Merus, PACT Pharma, RAPT, Rgenix and Tango. R.J. Sullivan: Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Personal, Advisory Board: Merck, Novartis, BMS, Eisai, Iovance, OncoSec, Pfizer, Replimmune; Financial Interests, Institutional, Funding, Clinical trial: GSK, Pfizer, Sanofi, Moderna, Roche-Genentech, BioMed Valley Discoveries, Astex, Deigene/Mapkure, Rubius. M.A. Mckean: Financial Interests, Institutional, Funding, Research funding: Acentage Pharma Group, Bicycle Therapeutics, Dragonfly Therapeutics, Epizyme, Exelixis, Genentech, GlaxoSmithKline, IDEAYA Biosciences, Ikena Oncology, Infinity Pharmaceuticals , Jacobio Pharmaceuticals, Moderna, NBE Therapeutics, Novartis, Oncorus, Plexx; Financial Interests, Institutional, Advisory Board, Consulting / Advisory Role: Array BioPharma, AstraZeneca, MedPage Today, Pfizer, Regeneron Pharmaceuticals. E.S. Santos: Financial Interests, Personal, Speaker’s Bureau: Genentech, Amgen, Lilly, Takeda, Pfizer, Novartis, Merck, Sanofigenzyme, Boehringer Ingelheim, Astrazeneca. K. Brill: Other, Personal, Full or part-time Employment: Pfizer. A. Polli: Other, Institutional, Full or part-time Employment: Pfizer ; Other, Institutional, Stocks/Shares: Pfizer . A. di Pietro: Financial Interests, Institutional, Full or part-time Employment: Pfizer. P.A. Ascierto: Financial Interests, Personal and Institutional, Advisory Board: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Personal and Institutional, Advisory Board: Roche-Genentech; Financial Interests, Personal and Institutional, Research Grant: Roche-Genentech; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal and Institutional, Advisory Board: Array; Financial Interests, Personal and Institutional, Research Grant: Array; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Advisory Board: Pierre-Fabre; Financial Interests, Personal, Advisory Board: Incyte; Financial Interests, Personal, Advisory Board: Medimmune; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Syndax; Financial Interests, Personal, Advisory Board: Sun Pharma; Financial Interests, Personal and Institutional, Advisory Board: Sanofi; Financial Interests, Personal and Institutional, Research Grant: Sanofi; Financial Interests, Personal, Advisory Board: Idera; Financial Interests, Personal, Advisory Board: Ultimovacs; Financial Interests, Personal, Advisory Board: Sandoz; Financial Interests, Personal, Advisory Board: Immunocore; Financial Interests, Personal, Advisory Board: 4SC; Financial Interests, Personal, Advisory Board: Alkermes; Financial Interests, Personal, Advisory Board: Italfarmaco; Financial Interests, Personal, Advisory Board: Nektar; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: Regeneron; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Oncosec; Financial Interests, Personal, Advisory Board: Nouscom; Non-Financial Interests, Institutional, Principal Investigator: Takis; Financial Interests, Personal, Advisory Board: Lunaphore; Financial Interests, Personal, Advisory Board: Seagen. All other authors have declared no conflicts of interest.