258 HORIZON-01: a phase I-III platform study evaluating the efficacy and safety of multiple therapies in patients with biomarker-defined locally advanced, unresectable stage III non-small cell lung cancer (NSCLC)

Abstract

Introduction [Formula presented] The standard of care for patients with stage III, unresectable NSCLC is chemoradiation (CRT) followed by durvalumab; however, some patients with driver-mutated tumours are unresponsive to immunotherapy. Multiple targeted therapies are approved for patients with advanced/metastatic NSCLC; we hypothesise that they may also be effective for patients with driver-mutated, unresectable, stage III NSCLC. Methods HORIZON-01 (BO42777; NCT05170204) is a phase I-III, global, open-label, randomised, platform study assessing the efficacy and safety of multiple targeted therapies versus durvalumab post-CRT, in patients with locally advanced, unresectable, stage III NSCLC selected according to their biomarker status (Figure). Biomarker eligibility is determined from local tissue testing or central testing via the BIOSTART study (NCT05419375). Eligible patients are randomised 1:1 to receive durvalumab (one year) or targeted therapy (three years) including alectinib (ALK+) or entrectinib (ROS1+), until disease progression, maximum treatment duration, unacceptable toxicity, consent withdrawal, or death. New cohorts may be added in future. Patients are aged >=18 years, with documented programmed cell death ligand 1 (PD-L1) status, >=2 cycles of prior concurrent/sequential CRT, and ECOG PS 0-2. Patients are stratified by disease stage (IIIA vs IIIB or IIIC), previous CRT type (concurrent vs sequential) and PD-L1 expression status (tumour cell score =1% vs unknown). Primary endpoint: progression-free survival by BICR (RECIST v1.1). Key secondary endpoints: distant metastasis-free survival, time to CNS progression, objective response rate, duration of response, overall survival, safety. Time to confirmed deterioration and patient-reported outcomes will be evaluated through questionnaires. Tumour assessments via CT/MRI will occur at screening, every 8 weeks for the first 48 weeks after treatment initiation, and then every 12 weeks. Enrolment is ongoing for cohort A1 (target: N = 120) at 168 locations globally, and closed for cohort A2. As of 22 November 2024, 55 patients have been randomised. Results N/A. Conclusions N/A. Disclosure Sanjay Popat: Leadership: BTOG Steering Committee, ETOP Foundation Council; Consulting or advisory role: Anheart, Amgen, Arcus Biosciences, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Daiichi Sankyo, Ellipses, Erasca, Gilead, GlaxoSmithKline, Guardant Health, IO Biotech, Janssen, Lilly, Merck KGaA, Mirati, MSD, Novartis, Novocure, Pfizer, PharmaMar, Pierre Fabre, Regeneron, Roche, Sanofi, Takeda, Turning Point Therapeutics. Adam Januszewski: No conflicts. Laura Cove-Smith: No conflicts. Shobhit Baijal: Consulting or advisory role: Abbvie, Agilent, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers-Squibb, Chugai, Daiichi Sankyo, FoundationOne, Gilead, GlaxoSmithKline, Janssen, Lilly, Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Pierre Fabre, Regeneron, Roche, Servier, Sanofi, Takeda; Speaker's Bureau: Abbvie, Agilent, Amgen, AstraZeneca, Bristol Myers-Squibb, FoundationOne, Gilead, Janssen, Lilly, Merck Serono, Novartis, Pfizer, Regeneron, Roche, Takeda; Travel, accommodation, expenses: Abbvie, AstraZeneca, Merck Sharp & Dohme, Regeneron, Roche, Takeda. Georgios Imseeh: Honoraria: AstraZeneca. Carl Gay: Consulting: Catalyst, Kisoji, STCube; Advisory board: Abdera, Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Daiichi Sankyo, G1, Jazz, Monte Rosa, Prophet, Roche/Genentech; Speaking engagement: ACHL, AstraZeneca, BeiGene, IDEOlogy, IDR, MJH, OncLive, PeerView, PER, Targeted Healthcare. Keith Kerr: Honoraria: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Janssen, Merck Serono, Merck Sharp & Dohme, Mirati, Novartis, Pfizer, Roche, Sanofi, Ventana, Medscape, Mirati, Prime Oncology, PeerVoice, PER; Consulting or advisory role: AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daichi Sankyo, Janssen, [Formula presented] Merck Serono, Merck Sharp & Dohme, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, Ventana. Terufumi Kato: Honoraria: Amgen, AstraZeneca, BeiGene, Boehringer Ingelheim, Bristol-Meyers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, Merck KGaA, MSD, Novartis, Ono, Pfizer, Taiho, Takeda; Advisory board: AstraZeneca, BeiGene, Chugai, Daiichi-Sankyo, Janssen, Merck KGaA, MSD, Novartis, Pfizer; Other (Employer [spouse]): Eli Lilly; Other (Institutional grants): Abbvie, Amgen, Arrivent, AstraZeneca, Bayer, BeiGene, BluePrint, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo, Eli Lilly, Gilead, GlaxoSmithKline, Haihe, Janssen, Merck KGaA, MSD, Novartis, Pfizer, Regeneron, Takeda. Luis Paz-Ares: Stock ownership: Altum Sequencing, STAb Therapeutics; Honoraria for Lectures: AstraZeneca, Janssen, Merck, Mirati, Sanofi; Consulting or advisory role: Lilly, MSD, Roche, Pharmamar, Merck KGaA (Darmstadt, Germany), AstraZeneca, Novartis, Pfizer, Sanofi, Bayer, BMS, Mirati, GSK, Janssen, Takeda, Regeneron, Sanofi, Gilead, Roche, Abbvie, Daichii; Travel, accommodation, expenses: Lilly, MSD, Roche, Pharmamar, Merck KGaA (Darmstadt, Germany), AstraZeneca, Novartis, Amgen, Pfizer, Sanofi, Bayer, BMS, Mirati, GSK, Janssen, Takeda, Regeneron. Caicun Zhou: Honoraria: Eli Lilly China, Roche, Merck Sharp & Dohme, Qilu, Hengrui, Innovent Biologics, Alice, LUYE Pharma, TopAlliance Biosciences Inc, Amoy Diagnostics, AnHeart, Johnson-Johnson, AmoyDx, Simcere Pharma; Consulting fees: Innovent Biologics, Qilu, Hengrui, TopAlliance Biosciences Inc. Karl Redhead: Current employment: Roche Products Ltd; Stock ownership: F. Hoffmann-La Roche Ltd. Elizabeth Theogaraj: Current employment: F. Hoffmann-La Roche Ltd; Stock ownership: F. Hoffmann-La Roche Ltd. Sarah M. Shagan: Current employment: Genentech, Inc.; Stock ownership: Roche. Benjamin J. Solomon: Current employment: Peter MacCallum Cancer Centre; Board of directors: International Association for the Study of Lung Cancer (IASLC), Thoracic Oncology Group of Australasia (TOGA), Cancer Council of Victoria; Honoraria: AstraZeneca, Merck Sharp & Dohme, Roche/Genentech, Pfizer, Amgen, Sanofi; Consulting or advisory role: Bristol-Myers Squibb, Meck Sharp & Dohme, AstraZeneca, Pfizer, Roche/Genentech, Amgen, Lilly, BeiGene, Takeda, GSK, Janssen; Royalties: UpToDate.