1107P - BRAF mutation status does not impact outcomes with tebentafusp in advanced cutaneous melanoma

Background

Tebentafusp (tebe), a bispecific (gp100 x CD3) ImmTAC, targets gp100 peptide-HLA-A*02:01 complexes overexpressed in melanoma. In a phase (Ph) 1b study (NCT02535078), pts with metastatic cutaneous melanoma (mCM) who relapsed or were refractory to prior anti-PD(L)1 and received tebe combined with durvalumab (durva) with or without tremelimumab (treme) (n=58), had a 1-year (yr) OS of 75%, comparing favorably with recent benchmarks (38%-57%) [1-3]. Nearly half of pts with mCM harbor activating BRAF mutations and sequencing of BRAF inhibitor regimens (BRAFi) with immunotherapies may be important [4]. Here we present tebe efficacy and safety in pts with mCM by BRAF mutation status.

Methods

In the Ph 1b study, HLA-A*02:01+, pre-treated mCM pts received weekly tebe (IV) monotherapy in arm 4 or in combination with durva and/or treme (IV) Q4W (arms 1-3). Primary objective was RP2D. Secondary objectives were safety and efficacy. OS was obtained using Kaplan-Meier methods. Tumor assessments were performed according to RECIST v1.1. This analysis was performed on all pts in arms 1-4 with data cut-off Oct 7 2022 and median follow up of 14.8 months.

Results

38/112 (34%) pts had an activating V600 BRAF mutation (BRAFm); of whom, 24 (63%) had received a prior BRAFi regimen. Baseline parameters (e.g., ECOG, LDH, anti-PD(L)1 exposure) were similar between the BRAFm and BRAF wild type (BRAFwt) pts. OS and tumor shrinkage were similar in BRAFm and BRAFwt pts with 1-yr OS of 68% and 62% and tumour shrinkage in 42% and 38% of pts, respectively. The safety profile of tebe was similar in BRAFm and BRAFwt pts. Among BRAFm pts, OS trended longer in those who did not receive prior BRAFi versus those who did (1-yr OS 84% vs 59%).

Conclusions

In this study, promising OS was seen in pretreated mCM pts with or without BRAFm, although OS trended longer in BRAFm pts who had not received prior BRAFi compared with those who did. An ongoing trial (NCT05549297) is investigating tebe as monotherapy and in combination with pembrolizumab in pts with previously treated advanced melanoma including both BRAFwt and BRAFm. 1. Zimmer L, et al. Eur J Cancer 75:47–55, 2017 2. Silva IPD, et al. J Clin Oncol 38:10005–10005, 2020 3. Arance AM et al. J Clin Oncol 39:S9504, 2021 4. Atkins MB, et al. J Clin Oncol 41(2):186-197, 2023.

Clinical trial identification

NCT02535078.

Editorial acknowledgement

Legal entity responsible for the study

Immunocore Ltd.

Funding

Immunocore Ltd.

Disclosure

A.N. Shoushtari: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Immunocore, Novartis; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb, Immunocore, Polaris, Xcovery, Pfizer, Novartis, Targovax ASA, Checkmate Pharmaceuticals, Linnaeus Therapeutics, Prelude Therapeutics; Financial Interests, Personal, Invited Speaker: Foghorn Therapeutics; Non-Financial Interests, Member: ASCO. M.R. Middleton: Financial Interests, Personal, Speaker, Consultant, Advisor: Bristol Myers Squibb, Immunocore, BioLineRx, Boehringer Ingelheim, Alkermes, Bayer; Financial Interests, Institutional, Research Funding: Immunocore, Novartis, AstraZeneca, Roche, Amgen, Bristol Myers Squibb, Merck, Pfizer, Replimune, Regeneron, GRAIL, BioLineRx, SalvaRx, Vaccitech, GRAIL; Non-Financial Interests, Personal, Other: GenesisCare. O. Hamid: Financial Interests, Personal, Advisory Board: Alkermes, Amgen, BMS, Bactonix, Beigene, Bioatla, Eisai, GSK, Georgiamune, GigaGen, Grit Bio, IO Biotech, Idera, Idera, Immunocore, Incyte, Instil Bio, Iovance, Janssen, KSQ, Merck, Nextcure, Novartis, Obsidian, Pfizer, Roche Genentech, Seagen, Sanofi/Regeneron, Tempus, Vial, Zelluna; Financial Interests, Personal, Invited Speaker: BMS, Immunocore, Novartis, Pfizer, Sanofi/Regeneron; Financial Interests, Personal, Stocks/Shares: Bactonix; Financial Interests, Institutional, Invited Speaker: Aduro, Akeso, Amgen, Arcus, BMS, Bioatla, CytomX, Exelixis, GSK, Idera, Immunocore, Incyte, Iovance, Merck, Merck Serono, Moderna, Nextcure, Novartis, Pfizer, Roche Genentech, Rubius, Seagen, Sanofi/Regeneron, Torque, Zelluna. F. Meier: Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, Bristol Myers Squibb, Novartis, MSD, Amgen, Merck, Sanofi, Pierre Fabre; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Novartis, Roche, Bristol Myers Squibb, MSD, Amgen, Merck, Sanofi, Pierre Fabre; Financial Interests, Personal, Other, Honoraria: Roche, Bristol Myers Squibb, Novartis, MSD, Amgen, Merck, Sanofi; Financial Interests, Institutional, Research Funding: Novartis, Roche. T. Bauer: Financial Interests, Personal, Full or part-time Employment: Tennessee Oncology; Financial Interests, Personal, Speaker, Consultant, Advisor: Pfizer, Bayer, Lilly, Sanofi; Financial Interests, Personal, Speaker’s Bureau: Bayer, Lilly; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Pfizer; Financial Interests, Institutional, Research Funding: Daiichi Sankyo, Incyte, Mirati Therapeutics, MedImmune, AbbVie, AstraZeneca, MabVax, Merck, Lilly, GSK, Novartis, Pfizer, Genentech/Roche, Immunogen, Immunocore, Roche, Bristol Myers Squibb, Amgen, Moderna Therapeutics, Sanofi, Boehringer Ingelheim, Astellas Pharma, Top Alliance BioScience, Loxo, Janssen, Takeda, Onyx, Foundation Medicine. A.K.S. Salama: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Iovance, Regeneron, Replimune, Novartis, Pfizer; Financial Interests, Institutional, Local PI: Bristol Myers Squibb, Ascentage, IDEAYA, Immunocore, Merck, Regeneron, Replimune, Seagen; Financial Interests, Institutional, Trial Chair: Olatec. J.M. Kirkwood: Financial Interests, Personal, Speaker, Consultant, Advisor: Novartis, Amgen, Harbour BioMed, ISTARI Oncology, Scopus BioPharma, Pfizer, AXIO Research, Immunocore, Natera, DermTech, Ankyra Therapeutics, Becker Pharmaceutical Consulting, Fenix Group International, IQVIA, Merck, Replimune, SR One Capital Management, Iovance Biotherapeutics, Checkmate Pharmaceuticals, OncoSec, OncoCyte, Cancer Network, Takeda, Applied Clinical Intelligence, PathAI, Magnolia Innovation, iOnctura, Jazz Pharmaceuticals, Regeneron; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Checkmate Pharmaceuticals, Bristol Myers Squibb, Regeneron, Ankyra Therapeutics, Iovance Biotherapeutics; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb; Financial Interests, Institutional, Research Funding: Amgen, Bristol Myers Squibb, Checkmate Pharmaceuticals, Immunocore, Iovance Biotherapeutics, Novartis, Immvira, Harbour BioMed, Takeda, Verastem, Lion Biotechnologies. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, MSD, Novartis, Merck Serono, Pierre Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Nektar, Boehringer Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant and Advisory Role, Travel support: Pfizer/Array; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Advisory Role: Eisai, Seagen; Financial Interests, Personal, Other, Consultant Role: Daiichi Sankyo, Pfizer, OncoSec, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role and travel support: Bio-AI Health; Financial Interests, Personal, Other, Consultant role: Medicenna; Financial Interests, Personal, Advisory Board, Consultant and Advisory Role: iTeos; Financial Interests, Personal, Advisory Board, Consultant and Advisory role: ValoTx; Financial Interests, Personal, Advisory Board, Consultant and Advisor role. 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Orloff: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker, Consultant, Advisor: IDEAYA Biosciences, Immunocore, Trisalus Life Sciences, Delcath Systems; Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, Immunocore, Delcath Systems, Plexxikon, IDEAYA Biosciences, Linnaeus Therapeutics, IDEAYA Biosciences. R. Edukulla, H. Goodall: Financial Interests, Personal, Full or part-time Employment: Immunocore; Financial Interests, Personal, Stocks/Shares: Immunocore. J.C. 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Evans: Financial Interests, Institutional, Advisory Board, Advisory Board for GI Cancers and Melanoma (Immune Checkpoint Inhibitors): Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker, Invited speaker - GI Cancers, Melanoma, Immunotherapy: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Board, Advisory Boards - GI cancers, melanoma: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Invited speaker GI cancer, melanoma: Roche/Genentech; Financial Interests, Institutional, Advisory Board, Advisory Board (lenvatinib): Eisai; Financial Interests, Institutional, Invited Speaker, Speaker's fees (lenvatinib): Eisai; Financial Interests, Institutional, Advisory Board, advisory board: MSD, AstraZeneca, Bayer, Bicycle Therapeutics, Clovis; Financial Interests, Institutional, Invited Speaker, Speaker's fees: MSD, AstraZeneca, Bayer; Financial Interests, Institutional, Advisory Board, Advisory board: Nucana; Financial Interests, Institutional, Invited Speaker, speaker's fees: Nucana; Financial Interests, Institutional, Advisory Board, advisory board; Chair of Scientific Advisory Council (HCC & MIV-818): Medivir; Financial Interests, Institutional, Invited Speaker, speaker's fees (and presentation to potential investors): Medivir; Financial Interests, Personal, Other, Support to attend international conferences: Bristol Myers Squibb, Roche/Genentech, MSD, Nucana, Bayer, Celgene, Pierre Fabre; Financial Interests, Institutional, Advisory Board, Advisory Board for Upper GI Cancer: Ascelia; Financial Interests, Institutional, Advisory Board, Advisory Board for Oesophageal Cancer: Seagen; Financial Interests, Institutional, Coordinating PI, Educational grant (supply of study agents) for investigator-led study and reimbursement of study costs for commercial studies: AstraZeneca; Financial Interests, Institutional, Local PI, reimbursement of study costs for commercial studies: Astellas, Bayer, Basilea, Celgene, GSK, Roche, Immunocore, Medivir, Starpharma, Novartis, Sapience Therapeutics, MiNa Therapeutics, Lilly, Bicycle Therapeutics, Sierra, CytomX, Beigene, Pfizer, Johnson & Johnson, UCB, Codiak, Avacta, Nurix, T3P; Financial Interests, Institutional, Coordinating PI, reimbursement of study costs for commercial studies: Adaptimmune, Bristol Myers Squibb, Eisai, MSD, Nucana, Sanofi, iOnctura; Financial Interests, Institutional, Local PI, support for non-commercial investigator-led study: Verastem; Financial Interests, Institutional, Local PI, reimbursement for costs of commercial studies: Boehringer Ingelheim; Financial Interests, Institutional, Local PI, reimbursement of costs of commercial study: Seagen; Non-Financial Interests, Member, Cancer Society Member: American Society of Clinical Oncology, America Association for Cancer Research, British Association for Cancer Research, Association of Cancer Physicians (UK), European Association for Cancer Research, International Liver Cancer Association; Non-Financial Interests, Other, Member of Scientific Advisory Panel: Pancreatic Cancer Research Fund; Non-Financial Interests, Other, Annual Meeting abstracts committee: International Liver Cancer Association; Non-Financial Interests, Institutional, Product Samples, Supply of investigational and licensed compounds for a non-commercial study for which I'm Chief Investigator: AstraZeneca; Other, Editor-in-Chief: British Journal of Cancer; Other, Chair of Independent Data Monitoring Committee for a phase I trial - honorarium payable to the employing institution: Genmab; Other, Chair and panel member, Scientific Evaluation Committee: Early phase trials (Amgen, Merck, AstraZeneca): Institut National du Cancer (France).