1320MO - Early evidence of efficacy in patients (pts) with non-small cell lung cancer (NSCLC) with HER2 exon20 insertion (ex20ins) mutations treated in a phase I study with BAY 2927088

Background

BAY 2927088, an oral, reversible, potent tyrosine kinase inhibitor, has anti-tumour activity against EGFR and HER2 mutations, including ex20ins, in preclinical models. Here we report preliminary safety and efficacy of BAY 2927088 in pts with EGFR- or HER2-mutant NSCLC.

Methods

This is an ongoing, open-label, multicentre, first-in-human, phase I trial. Eligible pts must have advanced NSCLC with an EGFR and/or HER2 mutation and disease progression after ≥1 systemic treatment. BAY 2927088 is orally administered daily in 21-day cycles and follows a Bayesian adaptive dose-selection model. Backfill is concurrent and includes escalation doses found to be safe and potentially efficacious. The primary objectives of the study are safety, tolerability, pharmacokinetics and maximum tolerated dose. Secondary objectives include the overall response rate (ORR) and the recommended phase II dose. Data cut-off was 18 August 2023.

Results

A total of 76 pts from the dose-escalation/backfill phases were evaluable for safety. 59% were female, median age 60 (range 35-81) years, and 72% never smokers. 97% of pts had received ≥1 systemic anti-cancer treatment. EGFR and HER2 ex20ins mutations were present in 18% and 26% of pts, respectively. Five dose-limiting toxicities were reported in 5 pts. Overall, 87%/25% of pts had drug-related any-grade/grade 3-4 treatment-emergent adverse events (TEAEs). No pts had drug-related TEAEs leading to treatment discontinuation. The most common drug-related TEAEs were diarrhoea (75%, mainly grade 1-2), paronychia (25%) and dry skin (22%). The ORR was 26% overall (18/69, including 4 unconfirmed partial responses [uPR]). Of note, the ORR was 60%, including 1 complete response, 8 PR and 3 uPR, in 20 evaluable pts with HER2 ex20ins mutant disease.

Conclusions

In an early phase I analysis of pts with EGFR- or HER2-mutant NSCLC, BAY 2927088 demonstrated a manageable safety profile up to 60 mg daily. In pts with HER2 ex20ins mutant disease, BAY 2927088 showed encouraging preliminary anti-tumour activity. These results warrant further investigation of BAY 2927088 in pts with NSCLC.

Clinical trial identification

NCT05099172.

Editorial acknowledgement

Medical writing and editorial assistance were provided by Complete HealthVizion.

Legal entity responsible for the study

Bayer AG.

Funding

Bayer AG.

Disclosure

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. G. Daniele: Financial Interests, Institutional, Research Grant, Grants or contracts: Gilead; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Gilead, GSK. T.A. Leal: Financial Interests, Personal, Other, All support for the present publication (e.g., funding, provision of study materials, medical writing, article processing charges, etc.): Bayer; Financial Interests, Institutional, Research Grant, Grants or contracts: Advaxis, Pfizer; Financial Interests, Personal, Other, Consulting fees: Jazz Pharmaceuticals, AstraZeneca, EMD Serono, Merck, Boehringer Ingelheim, Blueprint, Bayer, Genentech, Lilly, Janssen, Mirati, Takeda, Daiichi Sankyo, Eisai, Novocure, Amgen, Roche, Regeneron; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Targeted Oncology, Opinions in Lung Cancer, SITC, OncLive, Aptitude Health, Cardinal Health, Ideo, Grace, Vindico, Peerview, Medscape, Curio, Larvol, ASTRO, I3 Health, UpToDate, Bioascend; Financial Interests, Personal, Advisory Board, Participation on a Data Safety Monitoring Board or Advisory Board: NCI CCR PD-L1 Committee, DSMB; Financial Interests, Personal, Leadership Role, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: GASCO Board Member. 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 Diagnostics Co., Ltd., AstraZeneca K.K., Bayer HealthCare Pharmaceuticals Inc., 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., Merck Biopharma Co., Ltd., Taiho Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: Janssen Pharmaceutical K.K., Medpace Japan K.K.; 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., Sumitomo Dainippon Pharma Co., Ltd., Spectrum Pharmaceuticals, 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.; Non-Financial Interests, Member: American Society of Clinical Oncology, The Japan Lung Cancer Society, Japanese Society of Medical Oncology, The Japanese Cancer Association. Y. Shinno: Financial Interests, Institutional, Research Funding: Ono Pharmaceutical, Janssen Pharmaceutical, Japan Clinical Research Operations, Taiho Pharmaceutical, Bayer; Financial Interests, Personal, Other, Honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Bristol Myers Squibb, Chugai Pharmaceutical, Ono Pharmaceutical, Eli Lilly Japan. K. Nishino: Financial Interests, Personal, Invited Speaker: Ono Pharmaceutical Co., Ltd., NSD, Amgen, Janssen Pharmaceutical K.K., Novartis Pharmaceuticals, Eli Lilly Japan, Takeda Pharmaceutical Co.,Ltd., Chugai Pharmaceutical, Nippon Boehringer Ingelheim, Nippon Kayaku; Financial Interests, Institutional, Other, Research grant: Ono Pharmaceutical Co., Ltd., Taiho Pharmaceutical Co., Ltd., MSD, AbbVie, Daiichi Sankyo Company, Limited, Amgen, Sanofi K.K., Janssen Pharmaceutical K.K., Novartis Pharmaceuticals, Pfizer, Eli Lilly, Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co.,Ltd., Chugai Pharmaceutical, Merus, AstraZeneca; Financial Interests, Institutional, Other, Research grant: Eisai Co., Ltd.; Financial Interests, Personal, Invited Speaker, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker, Advisory Board: Merck Biopharma Co., Ltd., AstraZeneca. T. Sakamoto: Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Eli Lilly Japan K.K., Chugai Pharmaceutical Co., Ltd., Merck KGaA, Kyowa Kirin Co., Ltd., Novartis Pharma K.K., AstraZeneca K.K., Janssen Pharmaceutical K.K., MSD K.K., Illumina K.K., Takeda Pharmaceutical Co., Ltd, Taiho Pharmaceutical Co., Ltd., Pfizer Japan Inc., Hisamitsu Pharmaceutical Co., Inc., Ono Pharmaceutical Co., Ltd.. E. Felip: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Bayer, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Gilead, GSK, Janssen, Merck Serono, Merck Sharp & Dohme, Novartis, Peptomyc, Regeneron, Sanofi, Takeda, Turning Point, Pfizer; Financial Interests, Personal, Invited Speaker: Amgen, Daiichi Sankyo, Genentech, Janssen, Medical Trends, Medscape, Merck Serono, PeerVoice, Pfizer, Sanofi, Takeda, Touch Oncology, AstraZeneca, Bristol Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck Sharp & Dohme; Financial Interests, Personal, Member of Board of Directors, Independent member: Grifols; Financial Interests, Institutional, Local PI, Clinical Trial: AstraZeneca AB, AbbVie, Amgen, Bayer Consumer Care AG, BeiGene, Boehringer Ingelheim GmbH, Bristol Myers Squibb International Corporation, Daiichi Sankyo Inc., Exelixis Inc., F. Hoffmann-La Roche Ltd., Genentech Inc., GSK Research and Development Limited, Janssen Cilag International NV, Merck Sharp & Dohme Corp, Merck KGAA, Mirati Therapeutics Inc, Novartis Pharmaceutica SA, Pfizer, Takeda Pharmaceuticals International; Non-Financial Interests, Leadership Role, President (2021-2023): SEOM (Sociedad Espanola de Oncologia Medica); Non-Financial Interests, Member, Member of Scientific Committee: ETOP (European Thoracic Oncology Platform); Non-Financial Interests, Member, Member of the Scientific Advisory Committee: CAC Hospital Universitari Parc Taulí. J.C. Ruffinelli: Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Pierre-Fabre, Amgen, Bristol Myers Squibb; Financial Interests, Personal, Other, Support for attending meetings and/or travel: Ipsen, Merck Sharp and Dohme, Merck, Advanced Accelerator Applications. N. Gallot: Financial Interests, Personal, Full or part-time Employment, I am employed by ClinBAY Ltd, a Contract Research Organization undertaking contracted statistical analyses for the study presented in the publication funded by Bayer: ClinBAY Ltd; Financial Interests, Personal, Full or part-time Employment, I am employed by ClinBAY Ltd, a Contract Research Organization undertaking contracted statistical analyses of other oncology studies funded by Bayer: ClinBAY Ltd; Financial Interests, Personal, Stocks/Shares, I hold stocks from the commercial entity: Sanofi. Z. Wang: Financial Interests, Personal, Full or part-time Employment: Bayer; Financial Interests, Personal, Stocks/Shares: Bayer. C. Chen: Financial Interests, Personal, Full or part-time Employment: Bayer. B. Brennan: Financial Interests, Personal, Full or part-time Employment: Bayer HealthCare Pharmaceuticals, Inc.; Financial Interests, Personal, Stocks/Shares: Bayer HealthCare Pharmaceuticals, Inc., Roche. S. Pu: Financial Interests, Personal, Full or part-time Employment: Bayer HealthCare Pharmaceuticals, Inc.. M. Kornacker: Financial Interests, Personal, Stocks/Shares: Bayer AG; Financial Interests, Personal, Full or part-time Employment: Bayer 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; Financial Interests, Institutional, Coordinating PI: Eli Lilly, EMD Serono, Regeneron, Janssen; Financial Interests, Institutional, Research Grant: Arrivent; Financial Interests, Institutional, Funding: Teligene. D.S.W. Tan: Financial Interests, Personal, Advisory Board: Amgen, Novartis, Boehringer Ingelheim, C4 Therapeutics, AstraZeneca, GSK, Takeda, Eisai, Guardant, Merck, Pfizer, Roche; Financial Interests, Institutional, Research Grant: AstraZeneca, Amgen, Pfizer, ACM Biolabs; Financial Interests, Personal, Steering Committee Member: Novartis. B. Goh: Financial Interests, Institutional, Other, Contract with my institution for clinical trial costs: Bayer AG; Non-Financial Interests, Personal, Non remunerated activity, Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Drug Advisory Committee, Ministry of Health, Singapore. All other authors have declared no conflicts of interest.