Abstract 102TiP
Background
First-line (1L) SoC for pts with HER2-mutation positive (HER2m+) NSCLC is platinum-based chemotherapy ± immunotherapy. To date, no targeted 1L treatments (txs) have been approved. Zongertinib is a HER2-selective tyrosine kinase inhibitor that binds to wild-type and mutated HER2, sparing EGFR. In Phase Ia of Beamion LUNG-1 (NCT04886804), zongertinib conferred objective response (OR)/disease control rates of 49/91% in pts with pretreated HER2 aberration-positive solid tumours, and 58/97% in those pts with HER2m+ NSCLC, with manageable safety with few EGFR-associated adverse events. Here, we describe Beamion LUNG-2 (NCT06151574), a phase III, randomised, controlled, open-label trial which will compare the efficacy and safety of 1L zongertinib with SoC in pts with HER2m+, locally advanced/metastatic non-squamous NSCLC.
Trial design
∼270 pts will be randomised 1:1 to receive either zongertinib or SoC. Key inclusion criteria: histologically/cytologically diagnosed advanced/metastatic non-squamous NSCLC; no prior systemic tx for locally advanced/metastatic disease; HER2 mutation in the TKD; ≥1 measurable lesion (RECIST 1.1). Key exclusion criteria: tumours that have alterations with available therapy, and radiotherapy/major surgery ≤4 weeks prior to randomisation. In the experimental arm, 120 mg oral zongertinib QD will be given in 21-day cycles. In the comparator arm, 500 mg/m2 intravenous pemetrexed chemotherapy plus either 75 mg/m2 cisplatin or Area Under the Curve 5 carboplatin, plus 200 mg pembrolizumab will be given on Day 1 q3w for four cycles, followed by 500 mg/m2 pemetrexed plus 200 mg pembrolizumab q3w for ≤35 cycles. In both arms, tx will continue until progressive disease (RECIST 1.1), undue toxicity, or other criteria are met. Primary endpoint: progression-free survival (RECIST 1.1). Secondary endpoints: OR (defined as best overall response of complete or partial response, RECIST 1.1); pt-reported outcomes (changes from baseline to Week 25); overall survival; and adverse events during the on-treatment period (CTCAE 5.0).
Clinical trial identification
NCT06151574.
Editorial acknowledgement
Medical writing support for the development of this abstract, under direction of the authors, was provided by Ellie Sherwood MPhil, of Ashfield MedComms, an Inizio Company, and funded by Boehringer Ingelheim.
Legal entity responsible for the study
Boehringer Ingelheim.
Funding
Boehringer Ingelheim.
Disclosure
Y. Wu: Financial Interests, Personal, Advisory Role: AstraZeneca, Roche, Boehringer Ingelheim, Takeda; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Lilly, Roche, Pfizer, Boehringer Ingelheim, MSD Oncology, Bristol Myers Squibb, Hengrui Pharmaceutical, BeiGene Beijing; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Roche, Pfizer, Bristol Myers Squibb. M.L. Johnson: Financial Interests, Institutional, Research Grant: AbbVie, Acerta, Adaptimmune, Amgen, Apexigen, Arcus Biosciences, Array BioPharma, ArriVent BioPharma, Artios Pharma, AstraZeneca, Atreca, BeiGene, BerGenBio, BioAtla, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera Biosciences, Carisma Therapeutics, Checkpoint Therapeutics, City of Hope National Medical Center, Corvus Pharmaceuticals, Curis, Daiichi Sankyo, CytomX, Dracen Pharmaceuticals, Dynavax, Lilly, Eikon Therapeutics, Elicio Therapeutics, EMD Serono, EQRx, Erasca, Exelixis, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, GSK, Gritstone Oncology, Guardant Health, Harpoon, Helsinn Healthcare SA, Hengrui Therapeutics, Hutchinson MediPharma, IDEAYA Biosciences, IGM Biosciences, Immunitas Therapeutics, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Kartos Therapeutics, LockBody Therapeutics, Loxo Oncology, Lycera, Memorial Sloan-Kettering, Merck, Merus, Mirati Therapeutics, Mythic Therapeutics, NeoImmune Tech, Neovia Oncology, Novartis, Numab Therapeutics, Nuvalent, OncoMed Pharmaceuticals, Palleon Pharmaceuticals, Pfizer, PMV Pharmaceuticals, Rain Therapeutics, RasCal Therapeutics, Regeneron Pharmaceuticals, Relay Therapeutics, Revolution Medicines, Ribon Therapeutics, Rubius Therapeutics, Sanofi, Seven and Eight Biopharmaceuticals, Shattuck Labs, Silicon Therapeutics, Stem CentRx, Syndax Pharmaceuticals, Taiho Oncology, Takeda Pharmaceuticals, Tarveda, TCR2 Therapeutics, Tempest Therapeutics, Tizona Therapeutics, TMUNITY Therapeutics, Turning Point Therapeutics, University of Michigan, Vyriad, WindMIL Therapeutics, Y-mAbs Therapeutics; Financial Interests, Institutional, Other, Consulting: AbbVie, Alentis Therapeutics, Amgen, Arcus Biosciences, Arrivent, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, D3 Bio Limited, Daiichi Sankyo, Fate Therapeutics, Genentech/Roche, Genmab, Genocea Biosciences, Gilead Sciences, GSK, Gritstone Oncology, Hookipa Biotech, Immunocore, Janssen, Jazz Pharmaceuticals, Lilly, Merck, Mirati Therapeutics, Molecular Axiom, Normunity, Novartis, Novocure, Pfizer, Pyramid Biosciences, Revolution Medicines, Sanofi-Aventis, SeaGen, Synthekine, Takeda Pharmaceuticals, VBL Therapeutics. R.A. Soo: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, J INTS BIO, Janssen, Lily, Merck, Merck Serono, Novartis, Pfizer, Puma, Roche, Taiho, Takeda, Thermo Fisher, Yuhan; Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim, Pfizer. N. Baktash: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. D. Maier: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. S. Eigenbrod-Giese: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. T. Yoshida: Financial Interests, Personal, Speaker’s Bureau: Novartis, AbbVie, Amgen, Daiichi Sankyo, AstraZeneca, MSD, Chugai, Astellas, Medpace, Boehringer Ingelheim, BMS, Ono, Merck; Financial Interests, Personal, Advisory Board: Pfizer, Novartis, MSD, Amgen, Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Novartis, AbbVie, Amgen, Daiichi Sankyo, AstraZeneca, MSD, Chugai, Astellas, Medpace, Boehringer Ingelheim, BMS, Ono, Merck; Financial Interests, Institutional, Principal Investigator: Novartis, AbbVie, Amgen, Daiichi Sankyo, AstraZeneca, MSD, Chugai, Astellas, Medpace, Boehringer Ingelheim, BMS, Ono, Merck.