A randomized phase III trial evaluating oral BAY 2927088, compared with standard of care, as first-line treatment of locally advanced or metastatic NSCLC harboring HER2-activating mutations (SOHO-02)

BackgroundActivating human epidermal growth factor receptor 2 (HER2) mutations account for approximately 2-4% of non-small cell lung cancer (NSCLC), but there are no first-line HER2-targeted therapies currently approved for patients (pts) with locally advanced or metastatic NSCLC harboring HER2-activating mutations. BAY 2927088 is an oral, reversible tyrosine kinase inhibitor that targets HER2 and mutant epidermal growth factor receptor and has demonstrated anti-tumor activity and a manageable safety profile in previously treated pts with NSCLC and HER2-activating mutations in the Phase I/II SOHO-01 trial (LBA8598 accepted at ASCO 2024). The SOHO-02 trial evaluates the efficacy and safety of BAY 2927088 as first-line therapy in pts with locally advanced or metastatic NSCLC with HER2-activating mutations.Trial designSOHO-2 is a Phase III, open-label, randomized multicenter trial of BAY 2927088 in pts with locally advanced or metastatic NSCLC with HER2-activating mutations. Eligibility criteria include pts aged ≥18 years with documented locally advanced or metastatic non-squamous NSCLC, documented activating mutation in the tyrosine kinase domain of HER2 in tumor tissue, measurable disease per RECIST v1.1, ECOG PS of 0 or 1, and adequate bone marrow, kidney, liver, coagulation, and cardiac function. 278 eligible pts will be randomized to oral BAY 2927088 (20 mg twice daily) or standard of care (SoC; pembrolizumab in combination with platinum-based chemotherapy [cisplatin or carboplatin] and pemetrexed) administered in 21-day cycles. The primary objective is to evaluate the effect of BAY 2927088 vs SoC on progression-free survival per RECIST v1.1 by blinded independent central review (BICR). Key secondary objectives are overall survival, overall response rate, and duration of response per RECIST v1.1 by BICR, and to assess the safety and tolerability of BAY 2927088 compared with SoC. Health-related quality of life and symptomatic side effects will be measured using the EORTC QLQ-C30, NSCLC-SAQ, and EQ-5D-5L, including VAS. First patient, first visit is in June 2024.Clinical trial identificationEU CT: 2024-511319-91-00; NCT to be provided at the time of the congress.Editorial acknowledgementRyan Staudt and Jane Beck of Complete HealthVizion, IPG Health Medical Communications, provided editorial support, funded by Bayer AG.Legal entity responsible for the studyBayer AG.FundingBayer AG.DisclosureA. Passaro: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Eli Lilly, Janssen, Pfizer, Roche, Bayer; Financial Interests, Personal, Invited Speaker: AstraZeneca, Boehringer Ingelheim, Janssen, Merck Sharp & Dohme, Mundipharma, Daiichi Sankyo, Medscape, eCancer; Financial Interests, Personal and Institutional, Steering Committee Member, Steering Committee Member PALOMA-3 trial: Janssen; Financial Interests, Institutional, Local PI: Daiichi Sankyo, Janssen; Financial Interests, Personal and Institutional, Local PI: MSD; Financial Interests, Personal and Institutional, Steering Committee Member: Arrivent, Bayer; Financial Interests, Institutional, Coordinating PI: Cullinan Oncology; Non-Financial Interests, Other, Scientific Commitee for Lung Cancer Guideline: AIOM; Non-Financial Interests, Officer, ESMO Council Member & Chair of Communication Committee: ESMO; Non-Financial Interests, Officer, Chair of Communication Committee: ESMO; Non-Financial Interests, Officer, Council Member: ESMO. J.C. Brase: Financial Interests, Personal, Full or part-time Employment: Bayer Consumer Care AG. J. Xu, L. Mongay Soler: Financial Interests, Personal, Full or part-time Employment: Bayer HealthCare Pharmaceuticals, Inc. K. Goto: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Amgen K.K., Takeda Pharmaceutical Co., Ltd., Eli Lilly Japan K.K., Amgen Inc., Amoy Diagnosties Co., Ltd., AstraZeneca K.K., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Guardant Health Inc., Merck Biopharma Co., Ltd., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Thermo Fisher Scientific K.K., Taiho Pharmaceutical Co., Ltd., Syneos Health Clinical K.K., Life Technologies Japan Ltd., Bayer U.S., Riken Genesis Co., Ltd.; Financial Interests, Personal, Advisory Board: Bayer HealthCare Pharmaceuticals Inc., Janssen Pharmaceutical K.K., Haihe Biopharma Co., Ltd.; Financial Interests, Personal and Institutional, Funding: Amgen Inc., Amgen K.K., AstraZeneca K.K., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Eli Lilly Japan K.K., Haihe Biopharma Co., Ltd., Ignyta, Inc., Janssen Pharmaceutical K.K., Kissei Pharmaceutical Co., Ltd., Kyowa Kirin Co., Ltd., Loxo Oncology, Inc., Medical & Biological Laboratories Co., Ltd., Merck Biopharma Co., Ltd., Merus N.V., MSD K.K., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sysmex Corporation., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Turning Point Therapeutics, Inc., Amgen Astellas BioPharma K.K., Bayer Yakuhin, Ltd., Blueprint Medicines Corporation., Life Technologies Japan Ltd., NEC Corporation., Novartis Pharma K.K., Craif Inc., Pfizer R&D Japan G.K., LSI Medience Corporation., Precision Medicine Asia Co., Ltd., Riken Genesis Co., Ltd., Xcoo, Inc.; Non-Financial Interests, Member: American Society of Clinical Oncology, The Japan Lung Cancer Society, Japanese Society of Medical Oncology, The Japanese Cancer Association.