624P - Belvarafenib in patients (pts) with BRAF class II or III alteration-positive tumours: TAPISTRY study

Background

BRAF class II and III alterations are found in a range of cancers and are resistant to approved type 1 BRAF inhibitors. We present efficacy and safety data for the potent and selective RAF inhibitor belvarafenib in pts with BRAF class II or III alteration-positive solid tumours from Cohorts I and J of the TAPISTRY study.

Methods

The TAPISTRY phase II, open-label study (NCT04589845) is evaluating the efficacy and safety of various therapies in pts with advanced/metastatic solid tumours. Pts were aged ≥12 years, with measurable disease by RECIST v1.1 and BRAF class II mutant/fusion positive/intragenic deletion (Cohort I) or class III mutant tumours (Cohort J), identified by next-generation sequencing. Pts received 400 mg oral belvarafenib twice daily in 28-day cycles. Tumour assessments were performed at screening, every 8 weeks for 1 year, and every 12 weeks after. Primary endpoint: objective response rate (ORR) by independent review committee (IRC). Key secondary endpoints: ORR by investigator; clinical benefit rate; progression-free survival; overall survival; safety.

Results

At data cutoff, 30 pts in Cohort I and 24 in Cohort J were evaluable for safety. In the efficacy-evaluable population there were 26 pts in Cohort I (12 tumour types; most common: colorectal and NSCLC [15% each]) and 23 in Cohort J (8 tumour types; most common: colorectal [39%]). After a median follow-up of 4.4 mos in Cohort I and 5.6 mos in Cohort J, there were no confirmed responses by IRC in either cohort (Table). Most common treatment-related adverse event was dermatitis acneiform (Cohort I: 43%; Cohort J: 25%). No new safety signals were identified.

Conclusions

In this study belvarafenib did not demonstrate antitumour activity in pts whose tumours had class II or III BRAF alterations. However, a number of pts had stable disease. Further studies are needed to understand the value of BRAF inhibition in the tumour-agnostic setting. The safety profile of belvarafenib was consistent with the known safety profile of the drug. Table: 624P

CI, confidence interval; (TR)AE, (treatment-related) adverse event

Clinical trial identification

NCT04589845.

Editorial acknowledgement

Third-party medical writing assistance was provided by Ella Spraggan, MRes, of Ashfield MedComms.

Legal entity responsible for the study

F. Hoffmann-La Roche Ltd.

Funding

F. Hoffmann-La Roche Ltd.

Disclosure

R. Dziadziuszko: Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, MSD, Amgen, Bristol Myers Squibb, GSK; Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Novartis, Pfizer, MSD, Amgen; Financial Interests, Personal, Local PI: MSD, Amgen, AstraZeneca, Roche, Bristol Myers Squibb, Ryvu Therapeutics, Takeda, Celon Pharma; Non-Financial Interests, Personal, Other: Novartis, Illumina. S. Damian: Non-Financial Interests, Personal, Membership or affiliation: ESMO, AIOM; Non-Financial Interests, Institutional, Advisory Board: Incyte Corporation, Nerviano Medical Sciences S.r.l., Pfizer Inc., Roche S.p.A. S. Gadgeel: Financial Interests, Personal, Advisory Role: AstraZeneca, Pfizer, Gilead, Boehringer Ingelheim, Arcus, Blueprint, BMS, Mirati, Genetech/Roche, Merck, Eisai, Eli Lilly, Takeda, GSK; Financial Interests, Personal, Other, Travel: Mirati, Merck. E. Garralda: Financial Interests, Personal, Full or part-time Employment: NEXT Oncology; Financial Interests, Personal, Local PI: Adaptimmune Llc, Affimed Gmbh, Amgen SA, Anaveon AG, AstraZeneca AB, Bicycletx Ltd, BioInvent International AB, Biontech SE, Biontech Small Molecules Gmbh, Boehringer Ingelheim International Gmbh, Catalym Gmbh, Cyclacel BioPharmaceuticals, Cytovation AS, Genmab B.V., Hifibio Therapeutics, Hutchison Medipharma Limited, Icon, Imcheck Therapeutics, Immunocore Ltd, Incyte Corporation, Incyte Europe Sàrl, Janssen-Cilag International NV, Janssen-Cilag SA, Laboratorios Servier SL, Medimmune Llc, Merck & Co, Inc, Merck Kgga, Novartis Farmacéutica, S.A, Peptomyc, Pfizer Slu, Relay Therapeutics, Replimmune, Ribon Therapeutics, Ryvu Therapeutics SA, Seattle Genetics Inc, Sotio as, Sqz Biotechnologies, Symphogen A/S, Taiho Pharma Usa In, T-Knife Gmbh, Cytomx, F.Hoffmann La Roche Ltd, F-Star Beta Limited, Genentech Inc; Financial Interests, Institutional, Research Funding: Novartis, Roche, Thermo Fisher, AstraZeneca, Taiho, BeiGene, Janssen; Financial Interests, Personal, Speaker, Consultant, Advisor: Roche, Ellipses Pharma, Boehringer Ingelheim, Janssen Global Services, Seattle Genetics, Thermo Fisher, MabDiscovery, Anaveon, Hengrui, Sanofi, Incyte, Medscape, Pfizer, Amgen; Financial Interests, Personal, Speaker’s Bureau: Merck Sharp & Dohme, Roche, Thermo Fisher, Novartis, SeaGen; Financial Interests, Personal, Stocks/Shares: 1TRIALSP. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Coordinating PI: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. M. Krzakowski: Financial Interests, Personal, Advisory Role: AstraZeneca, Ipsen, Roche; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Ipsen, Roche, BMS, MSD; Financial Interests, Personal, Other, Travel and expenses: Takeda, AstraZeneca, Gilead, Roche, Amgen; Financial Interests, Personal, Other, Consulting: AstraZeneca, Ipsen Roche. C. Lin: Financial Interests, Personal, Other, Travel support: BeiGene, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Blueprint Medicines, Bristol Myers Squibb, Daiichi Sankyo, Novartis, AbbVie, PharmaEngine, Merck KGaA, Boehringer Ingelheim, Anbogen, IMPACT Therapeutics; Financial Interests, Personal, Invited Speaker: Eli Lilly, Novartis, Roche; Financial Interests, Personal, Other, Travel Support: IMPACT Therapeutics; Financial Interests, Institutional, Other, Local principal investigator: Nuvalent. D. Thomas: Financial Interests, Personal, Full or part-time Employment: Omico UNSW Garvan Institute; Financial Interests, Personal, Advisory Role: Roche, AstraZeneca, Pfizer, Eisai, Illumina, BeiGene, Elevation Oncology, RedX Pharmaceuticals, SunPharma, Bayer, AbbVie, George Clinical, Janssen, Merck, Kinnate, Microba, BioTessellate, Australian Unity, Foundation Medicine, Guardant, Intervenn, Amgen, Seattle Genetics and Eli Lilly ; Financial Interests, Personal, Research Funding: Omico, NHMRC; Financial Interests, Personal, Other, Travel: Roche. W. Kirschbrown, S. Patel, T. Pham, F. Wu: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc. M. Sbirnac: Financial Interests, Personal, Full or part-time Employment: F. Hoffmann-La Roche Ltd. F. Barlesi: Financial Interests, Institutional, Other: AbbVie, ACEA, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eisai, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd, Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, Medimmune, Merck, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis; Non-Financial Interests, Personal, Other: AbbVie, ACEA, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb, Boehringer Ingelheim, Eisai, Eli Lilly Oncology, F. Hoffmann-La Roche Ltd, Genentech, Ipsen, Ignyta, Innate Pharma, Loxo, Novartis, Medimmune, Merck, MSD, Pierre Fabre, Pfizer, Sanofi-Aventis. All other authors have declared no conflicts of interest.