Meeting
2023 ASCO Annual Meeting
Encorafenib (enco) + binimetinib (bini) + pembrolizumab (pembro) for unresectable locally advanced or metastatic BRAF V600-mutant melanoma: Results from STARBOARD safety lead-in (SLI).
Authors
Dirk Schadendorf
University Hospital Essen, Essen, Germany
Dirk Schadendorf , Reinhard Dummer , Caroline Robert , Antoni Ribas , Ryan J. Sullivan , Timothy J. Panella , Meredith McKean , Edgardo S. Santos , Jill S. Clancy , Mahgull Nazar Thakur , Anna Polli , Alessandra Di Pietro , Paolo Antonio Ascierto
Organizations
University Hospital Essen, Essen, Germany, University Hospital Zurich, Zurich, Switzerland, Gustave Roussy, Villejuif, France, Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, Massachusetts General Hospital, Boston, MA, University of Tennessee Medical Center at Knoxville, Knoxville, TN, Sarah Cannon Research Institute, Tennessee Oncology, Nashville, TN, Genesis Care US, Aventura, FL, Pfizer, Inc., Cambridge, MA, Pfizer, Inc., Sandwich, United Kingdom, Pfizer, Inc., Milano, Italy, Pfizer, Inc., Milan, Italy, Instituto Nazionale Tumori IRCCS – Fondazione Pascale, Naples, Italy
Research Funding
Pharmaceutical/Biotech Company
Pfizer Inc.
Background: BRAF inhibitors (BRAFi) + MEK inhibitors (MEKi) (eg, enco + bini) and immune checkpoint inhibitors (CPIs) (eg, pembro) are approved for patients (pts) with BRAF V600-mutant metastatic melanoma. Combinations of BRAFi + MEKi with CPIs further improve outcomes and may offer additional treatment strategies. STARBOARD (NCT04657991) is an ongoing randomized, double-blinded, placebo-controlled, phase 3 study of enco + bini + pembro vs pembro in pts with unresectable locally advanced or metastatic BRAF V600-mutant cutaneous melanoma. Here we present the SLI results. Methods: Key inclusion criteria were histologically confirmed unresectable/metastatic BRAF V600E/K-mutant cutaneous melanoma and ≤1 prior systemic therapy for unresectable/metastatic disease. Pts received enco 450 mg QD + bini 45 mg BID + pembro 200 mg IV Q3W (COMBO450+P) or enco 300 mg QD + bini 45 mg BID + pembro 200 mg IV Q3W (COMBO300+P). The primary objective was to identify the recommended phase 3 dose (RP3D). The primary endpoint was dose-limiting toxicity (DLT) incidence; secondary endpoints included safety, objective response rate (ORR), time to response (TTR), and PFS (post hoc). Results: 20 pts received COMBO450+P and 17 COMBO300+P (cutoff: Dec 2, 2022). See table for baseline characteristics. 1 pt had a DLT with COMBO450+P: Grade (G) 3 drug-induced liver injury with concurrent G4 ALT increase and G3 bilirubin increase that resolved. 2 pts had DLTs with COMBO300+P: 1 with G3 rheumatoid arthritis flare and 1 with inability to receive drug due to G4 arthralgia, G4 back pain, G4 pyrexia, G3 chills, G3 headache, G3 paranesthesia, and G3 maculopapular rash. Drug-related AEs led to permanent discontinuation in 4, 5, and 6 pts for enco, bini, and pembro, respectively. 1 pt in the COMBO300+P arm died <28 days after discontinuing all study treatments due to disease progression. See table for antitumor activity data. Conclusions: Safety across cohorts was comparable and consistent with the known safety profile of each agent. Both regimens were generally tolerable; COMBO450+P was chosen as the RP3D based on the totality of the safety data. The phase 3 portion of STARBOARD is ongoing. Clinical trial information: NCT04657991.
| COMBO450+P | COMBO300+P | |
|---|---|---|
| Baseline characteristics | n=20 | n=17 |
| Median age, y | 51.5 | 54.0 |
| ECOG PS 0, n (%) | 15 (75.0) | 15 (88.2) |
| BRAF V600E (local test), n (%) | 18 (90.0) | 14 (82.4) |
| Prior adjuvant BRAFi/MEKi, n (%) | 2 (10.0) | 0 |
| Prior adjuvant CPI, n (%) | 2 (10.0) | 0 |
| Median FU, months | 9.7 | 10.9 |
| Antitumor activity | n=19 | n=16 |
| ORR, n (%) [95% CI] | 12 (63.2) [41.0, 80.9] | 8 (50.0) [28.0, 72.0] |
| CR | 1 (5.3) | 1 (6.3) |
| PR | 11 (57.9) | 7 (43.8) |
| SD | 4 (21.1) | 3 (18.8) |
| PD | 0 | 1 (6.3) |
| Not evaluable | 3 (15.8) | 4 (25.0) |
| Response duration ≥6 mo, n (%) | 6 (50) | 6 (75) |
| Median TTR, wk | 9.0 | 9.2 |
| Median PFS, mo (95% CI) Pts at risk, n Pts with event, n (%) | 9.2 (7.1, NE) 20 7 (35) | NE (4.8, NE) 17 6 (35.3) |
NE, not estimable.
Disclaimer
This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org
Abstract Details
Session Type
Poster Session
Session Title
Melanoma/Skin Cancers
Track
Melanoma/Skin Cancers
Sub Track
Advanced/Metastatic Disease
Clinical Trial Registration Number
NCT04657991
Citation
J Clin Oncol 41, 2023 (suppl 16; abstr 9531)
DOI
10.1200/JCO.2023.41.16_suppl.9531
Abstract #
9531
Poster Bd #
294
Abstract Disclosures
Similar Abstracts
Abstract
2023 ASCO Annual Meeting
A phase 3 study (TILVANCE-301) to assess the efficacy and safety of lifileucel, an autologous tumor-infiltrating lymphocyte cell therapy, in combination with pembrolizumab compared with pembrolizumab alone in patients with untreated unresectable or metastatic melanoma.
First Author: Daniel Olson
First Author: Igor Tsaur
Abstract
2023 ASCO Annual Meeting
A phase 3 trial of fianlimab (anti–LAG-3) plus cemiplimab (anti–PD-1) versus pembrolizumab in patients with previously untreated unresectable locally advanced or metastatic melanoma.
First Author: Ana Baramidze
Abstract
2023 ASCO Annual Meeting
A phase 2 study of alrizomadlin (APG-115) in combination with pembrolizumab in patients with unresectable or metastatic cutaneous melanoma that has failed immuno-oncologic (IO) drugs.
First Author: Montaser F. Shaheen