3O - Phase I/II SOHO-01 study of BAY 2927088 in patients with previously treated HER2-mutant NSCLC: Safety and efficacy results from 2 expansion cohorts

Background

BAY 2927088 is a potent, oral, reversible HER2 tyrosine kinase inhibitor that has shown manageable safety and anti-tumor activity in patients (pts) with advanced non-small cell lung cancer (NSCLC) with HER2-activating mutations. Here, we report results from 2 expansion cohorts of the ongoing, open-label, multicenter Phase I/II SOHO-01 study (NCT05099172).

Methods

Pts with advanced NSCLC with HER2-activating mutations who had disease progression after ≥1 systemic therapies and were either naïve to HER2-targeted therapy (Cohort D) or previously treated with HER2-targeted antibody-drug conjugates (ADCs) (Cohort E) received oral BAY 2927088 20 mg twice daily. The primary objective was safety (MedDRA v27.0) and secondary objectives included antitumor activity (RECIST v1.1).

Results

As of October 14, 2024, 44 pts (D) and 34 pts (E) were treated. Median age was 62.0 years (D) and 62.5 years (E), 63.6% (D) and 61.8% (E) of pts were female, 70.5% (D) and 64.7% (E) had never smoked, 54.5% (D) and 76.5% (E) had received ≥2 therapy lines, and 82.4% (E) had received trastuzumab deruxtecan. All pts were included in the safety and efficacy analysis. Treatment-related adverse events (TRAEs) were reported in 97.4% of pts; diarrhea was the most common TRAE leading to dose reduction but no pts discontinued treatment due to diarrhea (Table). There were no cases of interstitial lung disease. The investigator-assessed objective response rate was 70.5% (95% CI 54.8, 83.2) in D and 35.3% (95% CI 19.7, 53.5) in E. The disease control rates (response or stable disease for ≥12 weeks) were 81.8% (D) and 52.9% (E). Median duration of response was 8.7 months (95% CI 4.5, not estimable [NE]) in D and 9.5 months (95% CI 4.1, NE) in E.

Conclusions

The safety profile of BAY 2927088was manageable across cohorts. Treatment with BAY 2927088 led to durable responses in pts naïve to HER2-targeted therapy and in those who had received a HER2-targeted ADC.

Clinical trial identification

NCT05099172; October 29, 2021.

Editorial acknowledgement

Medical writing and editorial assistance provided by Complete HealthVizion, IPG Health Medical Communications.

Legal entity responsible for the study

Bayer AG.

Funding

Bayer AG.

Disclosure

N. Girard: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Regeneron, AbbVie, Amgen, Lilly, Takeda, Owkin, Leo Pharma, Daiichi Sankyo, Ipsen, Pierre Fabre, Beigene; Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Pfizer, Amgen, MSD, Sanofi, Gilead, Janssen; Financial Interests, Personal, Officer: edimark; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS, Leo Pharma; Financial Interests, Institutional, Research Grant: MSD; Other, Personal, Other, Family member is an employee: AstraZeneca. H.H.F. Loong: Financial Interests, Institutional, Invited Speaker: Boehringer-Ingelheim, MSD; Financial Interests, Personal, Invited Speaker: Eli-Lilly, Illumina, Bayer, Guardant Health; Financial Interests, Personal, Advisory Board: Novartis, Takeda. B. Goh: Financial Interests, Institutional, Invited Speaker: MSD, Adagene, Bayer, Pfizer; Financial Interests, Institutional, Advisory Board: Bayer Healthcare; Financial Interests, Personal, Other, Consultancy: Adagene pharmaceutical; Financial Interests, Institutional, Research Grant, Support for investigator initiated trial: MSD; Financial Interests, Institutional, Other, Pharmaceutical support for clinical trial: BMS; Financial Interests, Institutional, Other, Pharmaceutical support for investigator initiated clinical trial: Taiho pharmaceuticals; Financial Interests, Institutional, Invited Speaker, Conducting clinical trial: alx; Financial Interests, Institutional, Invited Speaker, Pharmaceutical phase 1 trial: Novartis; Non-Financial Interests, Institutional, Other, Lead clinical trial platform of the Singapore Translational Cancer Consortium: Consortium for Clinical Research and Innovation Singapore; Non-Financial Interests, Personal, Member: ASCO. P.A. Jänne: Financial Interests, Personal, Advisory Board, Consulting fees for advice on drug development: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche/Genentech, Chugai Pharmaceuticals, Eli Lilly, Voronoi, Daiichi Sankyo, Novartis, Sanofi, Takeda Oncology, Mirati Therapeutics, Trasncenta, Silicon Therapeutics, Syndax, Nuvalent, Bayer, Esai, Allorion Therapeutics, Accutar Biotech, AbbVie, Duality Biologics, Blueprint Medicines, Dizal Pharma; Financial Interests, Personal, Advisory Board, Consulting fees for advice on diagnostic development: Biocartis; Financial Interests, Personal, Advisory Board, Consulting fee for advice on drug development: Merus, Frontier Medicines; Financial Interests, Personal, Advisory Board, Consulting fees for advice on drug development.: Hongyun Biotechnology; Financial Interests, Personal, Stocks/Shares: Gatekeeper Pharmaceuticals, Allorion Therapeutics, Frontier Medicines; Financial Interests, Personal, Royalties, I receive postmarketing royalties from being an inventor on a DFCI owned patent on EGFR mutations licensed to Lab Corp: Lab Corp; Financial Interests, Institutional, Research Grant, Sponsored research agreement with my institution: AstraZeneca, Daiichi Sankyo, PUMA, Eli Lilly, Boehringer Ingelheim, Revolution Medicines, Takeda Oncology. S. Novello: Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Speaker’s Bureau: AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Boehringer, Ingelheim, Bristol Myers Squibb, Janssen, Lilly, MSD, Novartis, Pfizer, Roche, Takeda; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: Sanofi. S. Lu: Financial Interests, Personal, Advisory Board: AstraZeneca, Pfizer, Hutchison MediPharma, ZaiLab, GenomiCare, Novarti, Yuhan Corporation, Menarini, Mirati Therapeutics Inc, Daiichi Sankyo, Inc., D3 Bio Limited, Simcere, Takeda and Roche; Non-Financial Interests, Personal, Member of Board of Directors: Innovent Biologics, inc.; Financial Interests, Personal, Research Grant: AstraZeneca, Hutchison, BMS, Heng Rui Beigene, Roche, Hansoh; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Roche, Hansoh. G. Daniele: Financial Interests, Personal, Invited Speaker: GSK, Gilead, Bayer; Financial Interests, Institutional, Research Grant: Gilead. H.R. Kim: Financial Interests, Personal, Speaker’s Bureau: ABL Bio, Ono Pharmaceutical, Roche/Genentech. K. Goto: Financial Interests, Personal, Advisory Role: Bayer AG; Financial Interests, Institutional, Research Grant: Amgen Inc., Amgen K.K., AstraZeneca K.K., Bayer Yakuhin, Ltd., Boehringer Ingelheim Japan, Inc., Bristol Myers Squibb K.K., Blueprint Medicines Corporation., 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., Life Technologies Japan Ltd., Loxo Oncology, Inc., Medical & Biological Laboratories Co, LTD., Merck Biopharma Co., Ltd., Merus N.V., MSD K.K., NEC Corporation., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sumitomo Dainippon Pharma Co., Ltd., Spectrum Pharmaceuticals, Inc., Sysmex Corporation., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Turning Point Therapeutics, Inc.; Financial Interests, Personal, Speaker’s Bureau: Amgen Inc., Amgen K.K., Amoy Diagnosties Co., Ltd., Amgen Astellas BioPharma K.K., AstraZeneca K.K., Bayer U.S., 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., Guardant Health Inc., Janssen Pharmaceutical K. K., Thermo Fisher Scientific K.K., Medpace Japan K.K., Merck Biopharma Co., Ltd., MSD K.K., Novartis Pharma K.K., Ono Pharmaceutical Co., Ltd., Otsuka Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: Amgen Inc., Janssen Pharmaceutical K.K., Eli Lilly Japan K.K. D.S.W. Tan: Financial Interests, Personal, Advisory Board: Amgen, Novartis, Boehringer Ingelheim, C4 Therapeutics, AstraZeneca, GSK, Takeda, Eisai, Guardant, Merck, Pfizer, Roche, Regeneron, Genmab; Financial Interests, Institutional, Research Grant: AstraZeneca, Amgen, Pfizer, ACM Biolabs; Financial Interests, Personal, Invited Speaker: Novartis. A. Prelaj: Financial Interests, Personal, Other, Training of personnel: AstraZeneca, Italfarma; Financial Interests, Personal, Invited Speaker, THE HIVE PROJECT: Discussant: Roche; Financial Interests, Personal, Advisory Board, Advisory board in Lung Cancer project: BMS; Financial Interests, Personal, Other, travel grant: Janssen; Financial Interests, Personal, Advisory Board: Janssen, AstraZeneca; Financial Interests, Personal, Invited Speaker: Medsir, Novartis, Lilly; Financial Interests, Institutional, Invited Speaker: Bayer, BMS, AstraZeneca, Lilly, MSD, Spectrum, Roche. M. Ghadessi: Financial Interests, Personal, Full or part-time Employment: Bayer Pharma AG. P. Grassi: Financial Interests, Personal, Full or part-time Employment: Bayer S.p.A. X. Le: Financial Interests, Personal, Advisory Board: AstraZeneca, Merck KGaA, Spectrum Pharmaceutics, Novartis, Boehringer Ingelheim, Eli Lilly, Hengrui, Janssen, Blueprint, Daiichi Sankyo, Regeneron, ArriVent, Abion, Pinetree therapeutics, AbbVie, Aviston, Allist, Bayer; Financial Interests, Institutional, Invited Speaker: Eli Lilly, EMD Serono, Regeneron, Janssen; Financial Interests, Institutional, Research Grant: Arrivent; Financial Interests, Institutional, Funding: Teligene. T.M. Kim: Financial Interests, Personal, Other, Consultancy: AstraZeneca, Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Janssen, Novartis, Takeda, Samsung Bioepis, Regeneron, Boryng; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca/MedImmune, Boryung, Hanmi, Janssen, Boehringer-ingelheim, Novartis, Takeda, Sanofi, Roche/Genentech, Merck Sharp & Dohme Corp, Merck Serono, Regeneron, Genmab, Bayer, RAPT Therapeutics, Blueprint Medicines Corporation, Black Diamond Therapeutics, AbbVie, Amgen, Beyondbio Inc, Fore Biotherapeutics, Dizal Pharmaceutical, Incyte Corporation, BeiGene. All other authors have declared no conflicts of interest.