922P - Dose expansion results of the bifunctional EGFR/TGFβ inhibitor BCA101 with pembrolizumab in patients with recurrent, metastatic head and neck squamous cell carcinoma

Background

Pembrolizumab (P) is approved for recurrent, metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). BCA101 is a first-in-class bifunctional EGFR/TGFβ inhibitor with a manageable safety profile and preliminary efficacy in advanced solid tumors ( ESMO 2022 731MO). Here we report the preliminary results from the fully enrolled expansion cohort combining BCA101+P as first line therapy in R/M HNSCC.

Methods

This ongoing single-arm, multicenter dose expansion cohort enrolled patients (pts) with R/M HNSCC, PD-L1 CPS≥1 with no prior systemic therapy for R/M disease, ECOG 0-1, and measurable disease (RECIST v1.1). Pts received BCA101 (1500 mg IV on days 1, 8, 15) with P (200 mg IV on day 1) every 21-days. Primary endpoint: safety; secondary endpoints: overall response rate (ORR), duration of response, progression-free survival (PFS), overall survival. Exploratory: molecular and immunologic predictors of response.

Results

Thirty-one of 33 pts were evaluable and each had at least two restaging scans. Pts were more often men (n=23, 70%); median age: 65 (range: 31-80). Eighteen (55%) had baseline PD-L1 CPS scores of 1-19, 15 (45%) were ≥20. Oropharynx (19, 58%) [12/19 (63%) HPV/p16+] and oral cavity (10, 30%) were the most common subsites. Twenty-five pts (76%) had distant disease. The ORR was 48% (1 CR, 14 PRs) with 65% (13/20) of HPV(-) pts achieving a response, including 5/10 (50%) responders with CPS 1-19. Median PFS has not been reached among HPV(-) pts with 13/20 responses ongoing (five >6 months). Grade 3+ treatment-related adverse events (TRAEs) were observed in 9/33 pts (27%). There were no treatment-related deaths. Acneiform rash was the most common TRAE of any grade (24/33, 73%). Response data for the full cohort (n=39) will be available at the time of the meeting.

Conclusions

BCA101+P exhibits encouraging anti-tumor activity particularly among HPV(-) pts, and the combination is well tolerated among this R/M HNSCC population. Further investigation is warranted.

Clinical trial identification

NCT04429542.

Editorial acknowledgement

Legal entity responsible for the study

Bicara Therapeutics.

Funding

Study funded by Bicara Therapeutics and conducted in collaboration with Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., USA.

Disclosure

G.J. Hanna: Financial Interests, Personal, Full or part-time Employment: Dana Farber Cancer Institute; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Merck, Kura Oncology, Sanofi, Prelude Therapeutics, Bicara Therapeutics, Naveris, Exicure, Remix Therapeutics, General Catalyst, Boxer Capital, Rain Therapeutics, KSQ Therapeutics, SIRPant Immunotherapeutics; Other, Personal, Expert Testimony: Aaronson Rappaport Feinstein & Deutsch, Ahmuty, Demers, & McMAnus, Wilson Elser Moskowitz Edelman & Dicker, LLP; Financial Interests, Personal, Financially compensated role: Bristol Myer Squibb, Kura Oncology; Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, Regeneron, Kartos Therapeutics, Exicure, GSK, Elevar Therapeutics, Genzyme, Kite/Gilead, NantKwest, Actuate Therapeutics, Bicara Therapeutics, Secura Bio; Financial Interests, Personal, Research Funding: Conquer Cancer, the ASCO Foundation, V Foundation, Gateway for Cancer Research. J. Kaczmar: Financial Interests, Personal, Advisory Role: Bicara Therapeutics, Rakuten Medical, Coherus Biosciences; Financial Interests, Personal, Stocks or ownership: HCA Healthcare; Financial Interests, Personal, Financially compensated role: Triangle Insight Group, The Scienomics Group. D.P. Zandberg: Financial Interests, Personal, Advisory Role: Blueprint Medicines, Macrogenics, Prelude Therapeutics, Merck; Financial Interests, Institutional, Research Funding: Merck, Bristol Myers Squibb, Macrogenics, Astellas Pharma, Aduro Biotech, EMD Serono, Exelixis, GSK, Bicara Therapeutics, Checkmate Pharmaceuticals, ISA Pharmaceuticals, Novasenta. D.J. Wong: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Genentech/Roche, Sanofi/Aventis, Blueprint Medicines, Regeneron; Financial Interests, Institutional, Research Funding: Merck Serono, Merck Sharp & Dohme, ARMO BioSciences, AstraZeneca/MedImmune, Kura Oncology, Regeneron, Genentech/Roche, Bristol Myers Squibb, F-Star, Pfizer, Astellas Pharma, Enzychem Lifesciences, Elevar Therapeutics, TopAlliance BioSciences Inc, Checkmate Pharmaceuticals, Bicara Therapeutics, Gilead Sciences; Financial Interests, Personal, Research Funding: Lilly. E. Yilmaz: Financial Interests, Personal, Advisory Role: Astellas Pharma. E.J. Sherman: Financial Interests, Personal, Advisory Role: Eisai, UpToDate, Lilly, Blueprint Medicines, Exelixis; Financial Interests, Institutional, Research Funding: Plexxikon, Regeneron, Lilly, HUTCHMED, Novartis. A. Hernando Calvo: Other, Personal, Other: Merck Serono, Kyowa Kirin International. A.G. Sacco: Financial Interests, Personal, Full or part-time Employment: Moores Cancer Center; Financial Interests, Personal, Advisory Role: Bicara Therapeutics; Financial Interests, Institutional, Research Funding: Merck, Bicara Therapeutics, Nektar. D. Bohr: Financial Interests, Personal, Full or part-time Employment: Bicara Therapeutics; Financial Interests, Personal, Stocks or ownership: Bicara Therapeutics, Bristol Myers Squibb Foundation, Johnson & Johnson/Janssen, Gilead Sciences. R. Reiners: Financial Interests, Personal, Full or part-time Employment: Bicara Therapeutics; Financial Interests, Personal, Stocks or ownership: Bicara Therapeutics. S. Bilic: Financial Interests, Personal, Advisory Role: Bicara Therapeutics. R. Salazar: Financial Interests, Personal, Full or part-time Employment: Bicara Therapeutics; Financial Interests, Personal, Stocks or ownership: Bicara Therapeutics. E. Gharakhani: Financial Interests, Personal, Full or part-time Employment: Bicara Therapeutics; Financial Interests, Personal, Stocks or ownership: Biogen, Bicara Therapeutics. C.H. Chung: Financial Interests, Personal, Advisory Role: Exelixis, Merck, Brooklyn ImmunoTherapeutics, Fulgent Pharma, Genmab; Financial Interests, Institutional, Research Funding: AstraZenecca, Bristol Myers Squibb, Lilly, Merck, Regeneron, Brooklyn ImmunoTherapeutics, Iovance Biotherapeutics.