Abstract 131TiP
Background
Durvalumab following chemoradiation (CRT) is a standard of care for stage III unresectable NSCLC, but there remains an unmet need for improved therapeutic options among pts with driver mutated tumours that are unresponsive to immunotherapy. As targeting of specific driver mutations (e.g., ALK, RET, ROS1) has proven effective in the metastatic setting, it is hypothesised that outcomes could also be improved for pts with driver-mutated stage III NSCLC.
Trial design
BO42777 is a phase I–III platform study evaluating the safety and efficacy of multiple targeted therapies vs durvalumab following CRT in pts with locally advanced, unresectable, Stage III NSCLC. Biomarker eligibility is determined via local tissue testing or central testing within the BX43361 master screening study. Biomarker-eligible pts are enrolled into the relevant cohort and randomised 1:1 to receive durvalumab or targeted therapy (alectinib [ALK+], entrectinib [ROS1+], or pralsetinib [RET fusion+]). New cohorts may be added in the future. Key inclusion criteria: locally advanced, unresectable Stage III NSCLC, age ≥18 years, ≥2 prior cycles of concurrent or sequential CRT (cCRT or sCRT), ECOG PS 0–2. Pts are stratified based on staging (IIIA vs IIIB or IIIC), CRT type (cCRT vs sCRT), and PD-L1 status (tumour cell score <1% vs ≥1% vs unknown) and will receive investigational treatment for 3 years or durvalumab for 1 year, until progression or maximum duration of treatment, unacceptable toxicity, consent withdrawal, or death. Primary endpoint: progression-free survival (RECIST v1.1) by blinded independent central review. Key secondary endpoints: distant metastasis-free survival, time to CNS progression, objective response rate, duration of response, overall survival, and safety (adverse events). Time to confirmed deterioration and patient-reported outcomes will be assessed through questionnaires. Tumour response will be assessed by CT/MRI imaging at regular intervals. Enrolment is ongoing (target of 320 pts) across 200 sites in 11 countries. As of 6 Jan 2023, 2 pts have been randomised.
Clinical trial identification
NCT05419375 & NCT05170204.
Editorial acknowledgement
These trials are sponsored by F. Hoffmann-La Roche Ltd. Medical writing support for the development of this abstract, under the direction of the authors, was provided by Olivia Barber, BSc and Laura Vergoz, PhD of Ashfield MedComms, an Inizio company, and funded by F. Hoffmann-La Roche Ltd.
Legal entity responsible for the study
F. Hoffmann-La Roche Ltd.
Funding
F. Hoffmann-La Roche Ltd.
Disclosure
L. Paz-Ares: Financial Interests, Personal, Other, Board member: Altum sequencing, Genomica, AECC; Financial Interests, Personal, Member: AECC, ASCO, ASEICA, ESMO, Small Lung Cancer Group; Financial Interests, Personal, Other, Speaker fees and/or advisory board: Amgen, AstraZeneca, Bayer, BeiGene, BMS, Daiichi Sankyo, GSK, Janssen, Eli Lilly, Medscape, Merck Serono, Mirati, MSD, Novartis, PER, Pfizer, PharmaMar, Roche, Sanofi, Takeda, AACR; Financial Interests, Personal, Other, Coordinating PI: Alkermes, Amgen, AstraZeneca, BMS, Daiichi Sankyo, Janssen-Cilag, Eli Lilly, Merck Sharp & Dohme corp., Novartis, Pfizer, PharmaMar, Roche, Sanofi, Takeda, Tesaro; Financial Interests, Personal, Other, Foundation president: ONCOSUR. C.M. Gay: Financial Interests, Personal, Speaker's Bureau: AstraZeneca, BeiGene; Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, G1 Therapeutics, Jazz Pharmaceuticals, MonteRosa Therapeutics; Financial Interests, Personal, Research Grant: AstraZeneca. C. Zhou: Financial Interests, Personal, Other, Consulting fees: Innovent Biologics, Qilu, Hengrui, TopAlliance Biosciences Inc; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Eli Lilly China, Sanofi, Boehringer Ingelheim, Roche, MSD, Qilu, Hengrui, Innovent Biologics, C-Stone LUYE Pharma, TopAlliance Biosciences Inc, Amoy Diagnositics, AnHeart. T. Kato: Financial Interests, Institutional, Research Grant: AbbVie, Amgen, AstraZeneca, Blueprint, Chugai, Eli Lilly, Haihe, Merck Biopharma, MSD, Novartis, Pfizer, Regeneron, Takeda; Financial Interests, Personal, Other, Honoraria for lectures, presentations or educational events: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Merck Biopharma, MSD, Novartis, Ono, Pfizer, Roche; Financial Interests, Personal, Other, Participation on a Data Safety Monitoring Board or Advisory Board: AbbVie, Amgen, AstraZeneca, BeiGene, Chugai, Daiichi-Sankyo, Eli Lilly, Glaxo, Merck Biopharma, MSD, Nippon Kayaku, Novartis, Ono, Pfizer, Taiho, Takeda. K. Redhead: Financial Interests, Personal, Full or part-time Employment: Roche Products Limited; Financial Interests, Personal, Stocks/Shares: Roche Products Limited. A. Rahman: Financial Interests, Personal, Full or part-time Employment: Roche Products Limited; Financial Interests, Personal, Stocks/Shares: Roche Products Limited. D. Bradley: Financial Interests, Personal, Full or part-time Employment: Roche Products Limited; Financial Interests, Personal, Stocks/Shares: Roche Products Limited; Financial Interests, Personal, Other, Named on Roche Products Limited patent: Roche Products Limited. E. Theogaraj: Financial Interests, Personal, Full or part-time Employment: Roche Products Limited. K.E. Hutchinson: Financial Interests, Personal, Full or part-time Employment: Roche/Genentech; Financial Interests, Personal, Stocks/Shares: Roche/Genentech. S.M. Shagan: Financial Interests, Personal, Full or part-time Employment: Roche/Genentech; Financial Interests, Personal, Stocks/Shares: Roche/Genentech. B.J. Solomon: Financial Interests, Personal, Invited Speaker: Roche, Pfizer, Bristol Myers Squibb, Merck Sharp Dohme, AstraZeneca, Eli Lilly, Amgen, Takeda; Financial Interests, Personal, Advisory Board: Roche, Pfizer, Novartis, Bristol Myers Squibb, Merck Sharp Dohme, Merck Serono, AstraZeneca, Eli Lilly, Amgen, Takeda, BeiGene; Financial Interests, Personal, Research Grant: Sanofi, Pfizer. All other authors have declared no conflicts of interest.