LBA5 - Zongertinib in patients with HER2-mutant NSCLC: Updated analysis of beamion LUNG-1

Background

Zongertinib (BI 1810631) is a novel, orally administered HER2 TKI that selectively and covalently binds to the HER2 TKD, while sparing wild-type EGFR, thereby avoiding associated toxicities. Beamion LUNG-1 (NCT04886804) is a Phase Ia/Ib first-in-human study evaluating safety and efficacy of zongertinib in pts with HER2-mutant NSCLC (Phase Ib). Here, we report updated Phase Ib Cohort 1 results, including previously unreported time-to-event data.

Methods

Phase Ib is recruiting pts with HER2-mutant advanced/metastatic NSCLC. In Cohort 1, pts with previously treated HER2 TKD-mutant NSCLC were initially randomized to receive zongertinib 120 mg or 240 mg QD in 21-day cycles; the 120 mg dose was selected at an interim analysis. Cohort 1 primary endpoint was objective response (best overall response of complete or partial response; RECIST v1.1) by blinded central independent review.

Results

At data cut-off (Aug 29, 2024), 75 pts had received zongertinib 120 mg; 28 (37%) had brain metastases. Median duration of treatment was 8.5 months (range, 1–15). The confirmed overall response rate (ORR) was 71%; disease control rate was 93%. The 6-month duration of response and PFS rates (KM estimate) were 73% (95% CI, 56–84) and 69% (95% CI, 57–79); 55% of responding patients remained on treatment at data cut-off. In 27 evaluable pts with brain metastases, ORR in CNS lesions was 37% (RANO-BM; central review). TRAEs were reported in 96% of pts: grade (G)1 in 37%, G2 in 41%, G3 in 16%, and G4 in 1% (no G5 events). The most common TRAE was diarrhea, reported in 51% of pts; G1 in 43%, G2 in 7%, and G3 in 1% (no G4/5 events). Other TRAEs (all/G ≥3) included ALT increased (20%/8%), AST increased (21%/5%), and rash (combined term; 27%/0%). There were no cases of interstitial lung disease (ILD). Two pts (3%) had AEs (any-cause) leading to discontinuation.

Conclusions

Treatment with zongertinib led to high response rates, including preliminary activity in the CNS, and encouraging duration of response and PFS in pts with HER2 TKD-mutant NSCLC. Zongertinib demonstrated a manageable safety profile, with most TRAEs being low-grade, including both diarrhea and rash.

Clinical trial identification

NCT04886804; 05/14/2021.

Editorial acknowledgement

Medical writing support for the development of this abstract was provided by Hannah Simmons, MSc, of Ashfield MedComms, an Inizio company.

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim.

Disclosure

N. Yamamoto: Financial Interests, Personal, Other, Honoraria: Chugai Pharma, Daiichi Sankyo/UCB Japan, Eisai; Financial Interests, Institutional, Research Funding: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers-Squibb, Carna Biosciences, Chiome Bioscience, Chugai Pharma, Cimic, Daiichi Sankyo, Eisai, Eli Lilly, Genmab, GSK, InventisBio, Janssen Pharma, Kaken, Kyowa Kirin, Pfizer, Merck, MSD, Novartis, ONO, Otsuka, Rakuten Medical, Shionogi, Sumitomo Pharma, Taiho, Takeda, Toray; Financial Interests, Personal, Speaker, Consultant, Advisor: Boehringer Ingelheim, Chugai Pharma, Cimic, Eisai, Healios, Merck, Mitsubishi Tanabe, Noile-Immune Biotech, Rakuten Medical, Takeda. H. Tu: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Boehringer Ingelheim, Eli Lilly , Roche, Pfizer . M. Ahn: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, Takeda, Roche, Daiichi Sankyo, MSD, Amgen, Merck, Gilead, Genexin, Alphapharmaceutical. K. Yoh: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Chugai, Lilly, Amgen, Takeda, Ono Pharmaceutical, MSD, Daiichi Sankyo, Kyowa Kirin; Financial Interests, Personal, Advisory Board: AbbVie, Boehringer Ingelheim; Financial Interests, Institutional, Local PI: AstraZeneca, Lilly, Daiichi Sankyo, AbbVie, Taiho Pharmaceutical, MSD, Takeda, Boehringer Ingelheim, Chugai, Amgen, ArriVent Biopharma; Financial Interests, Personal, Steering Committee Member: AstraZeneca. J. Zugazagoitia: Financial Interests, Personal, Advisory Role: Merck, Sanofi, Pfizer, BMS, Novartis; Financial Interests, Personal, Financially compensated role: Janssen, MSD; Financial Interests, Institutional, Funding: AstraZeneca, BMS, Roche; Financial Interests, Personal, Invited Speaker: Pfizer, Takeda, Pierre Fabre, NanoString, Diagnostica Longwood, MSD; Financial Interests, Institutional, Research Funding: AstraZeneca, BMS, Roche; Financial Interests, Institutional, Research Grant: Roche, BMS, AstraZeneca; Financial Interests, Personal, Speaker, Consultant, Advisor: Pfizer, Takeda, Pierre Fabre, NanoString, Diagnostica Longwood, MSD, BMS, AstraZeneca, Janssen, Roche. E.F. Smit: Financial Interests, Institutional, Advisory Board: AstraZeneca, Daiichi Sankyo, MSD, Boehringer Ingelheim, Roche, Eli Lilly, Takeda, Sanofi, Janssen, BMS; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Merck Seranno; Financial Interests, Institutional, Other, DSMB member: DSI; Financial Interests, Institutional, Local PI: Pfizer, AZ, Genmab, DSI, Sanofi. Y. Wu: Non-Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, Boehringer Ingelheim, Pfizer, Roche; Financial Interests, Personal, Speaker, Consultant, Advisor, Honoraria: AstraZeneca, BeiGene Beijing, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Hengrui Pharmaceutical, MSD Oncology, Pfizer, Roche. D. Planchard: Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, AbbVie, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly, Takeda, Daiichi Sankyo, Merck, Novartis, ArriVent, Janssen, Pfizer, Roche, Pierre Fabre, Mirati, Seagen, GSK; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, Roche, Novartis, Pfizer; Financial Interests, Institutional, Principal Investigator: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Eli Lilly, Merck, Novartis, Pfizer, Roche, Medimmun, Sanofi-Aventis, Taiho Pharma, Novocure, Daiichi Sankyo, AbbVie, Janssen, Pierre Fabre, Takeda, ArriVent, Mirati, Seagen. B.C. Cho: Financial Interests, Personal, Advisory Board: KANAPH Therapeutic Inc, Bridgebio therapeutics, Cyrus therapeutics, Guardant Health, Oscotec Inc, J INTS Bio, Therapex Co., Ltd, Gilead, Amgen; Financial Interests, Personal, Full or part-time Employment: Yonsei University Health System; Financial Interests, Personal, Invited Speaker: AstraZeneca, Guardant, Roche, Korean Cancer Association, Korean Society of Medical Onoclogy, Korean Society of Thyroid-Head and Neck Surgery, Korean Cancer Study Group, Pfizer, Novartis, MSD, The Chinese Thoracic Oncology Society; Financial Interests, Personal, Licencing Fees: Champions Oncology, Crown Bioscience, Imagen, PearlRiver Bio GmbH; Financial Interests, Personal, Member of Board of Directors: J INTS BIO; Other, Personal, Other, Founder: DAAN Biotherapeutics; Financial Interests, Institutional, Research Grant: MOGAM Institute, LG Chem, Oscotec, Interpark Bio Convergence Corp, GIInnovation, GI-Cell, Abion, AbbVie, AstraZeneca, Bayer, Blueprint Medicines, Boehringer Ingelheim, Champions Onoclogy, CJ bioscience, CJ Blossom Park, Cyrus, Dizal Pharma, Genexine, Janssen, Eli Lilly, MSD, Novartis, Nuvalent, Oncternal, Ono, Regeneron, Dong-A ST, Bridgebio therapeutics, Yuhan, ImmuneOncia, Illumina, Therapex, Kanaph therapeutics, JINTSbio, Hanmi, CHA Bundang Medical Center, Vertical Bio AG; Financial Interests, Personal, Speaker, Consultant, Advisor: Abion, BeiGene, Novartis, AstraZeneca, Boehringer-Ingelheim, Roche, BMS, CJ, CureLogen, Cyrus therapeutics, Ono, Onegene Biotechnology, Yuhan, Pfizer, Eli Lilly, GI-Cell, Guardant, HK Inno-N, Imnewrun Biosciences Inc., Janssen, Takeda, MSD, Janssen, Medpacto, Blueprint medicines, RandBio, Hanmi; Financial Interests, Personal, Stocks/Shares: TheraCanVac Inc, Gencurix Inc, Bridgebio therapeutics, KANAPH Therapeutic Inc, Cyrus therapeutics, Interpark Bio Convergence Corp., J INTS BIO. B. Wehler: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim Pharma GmbH & Co. KG (Germany); Financial Interests, Personal, Advisory Role: Boehringer Ingelheim Pharma GmbH & Co. KG (Germany); Financial Interests, Institutional, Local PI: Boehringer Ingelheim GmbH; Financial Interests, Institutional, Research Funding: Boehringer Ingelheim Pharma GmbH & Co. KG (Germany). E. Nadal: Financial Interests, Personal, Advisory Board: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Boehringer Ingelheim, Lilly, Pfizer, Merck Serono, Daiichi Sankyo, AstraZeneca, Takeda, Amgen, Sanofi, Qiagen, Janssen, Regeneron, Pierre Fabre; Financial Interests, Personal, Invited Speaker: Roche, Bristol Myers Squibb, Merck Sharp Dohme, Lilly, Pfizer, Sanofi, AstraZeneca, Takeda, Amgen, Qiagen, Janssen, Daiichi, Illumina; Financial Interests, Personal and Institutional, Funding, Clinical trial funded by Roche: Roche; Financial Interests, Personal and Institutional, Funding, Merck Serono funded a clinical trial: Merck Serono; Financial Interests, Personal and Institutional, Funding, BMS funded a clinical trial: Bristol Myers Squibb; Non-Financial Interests, Personal, Advisory Role: Pfizer, Roche, Apollomics, Transgene; Other, Personal, Other, Member of the Steering Committee: Spanish Lung Cancer Group (GECP). U. von Wangenheim: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. M. Rohrbacher, B. Sadrolhefazi: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. J. Heymach: Financial Interests, Personal, Advisory Board: AbbVie, AnHeart Therapeutics, ArriVent Biopharma, AstraZeneca, BioCurity Pharmaceuticals, BioNTech AG, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Chugai Pharmaceutical, Curio Science, DAVA Oncology, Eli Lilly & Co, EMD Serono, Genentech, GSK, IDEOlogy Health, Immunocore, InterVenn Biosciences, Janssen Biotech, Janssen Pharmaceuticals, Mirati Therapeutics, Moffitt Cancer Center, ModeX, Novartis Pharmaceuticals, Roche, Regeneron Pharmaceuticals, OncoCyte, Sanofi, Takeda, RefleXion, uniQure, Spectrum Pharmaceuticals, Nexus Health Systems; Financial Interests, Personal, Speaker, Consultant, Advisor: Sandoz Pharmaceutical, Spectrum Pharmaceuticals, uniQure, RefleXion, Takeda, Sanofi, OncoCyte, Regeneron Pharmaceuticals, Roche, Sandoz Pharmaceutical, Nexus Health Systems, Novartis Pharmaceuticals, ModeX, Moffitt Cancer Center, Mirati Therapeutics, Janssen Pharmaceuticals, Janssen Biotech, InterVenn Biosciences, Immunocore, IDEOlogy Health, GSK, Genentech, EMD Serono, Eli Lilly & Co, DAVA Oncology, Curio Science, Chugai Pharmaceutical, Bristol Myers Squibb, Boehringer Ingelheim, Blueprint Medicines, BioNTech AG, BioCurity Pharmaceuticals, AstraZeneca, ArriVent Biopharma, AnHeart Therapeutics, AbbVie; Financial Interests, Personal, Full or part-time Employment: MD Anderson Cancer Center; Financial Interests, Personal and Institutional, Licencing Fees: Spectrum; Financial Interests, Personal and Institutional, Membership or affiliation: ASCO, IASLC, AACR, ESMO, ASCI, AAP, NRG, SWOG, AAS; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Boehringer-Ingelheim, Mirati, Bristol-Myer Squibb, Takeda; Financial Interests, Institutional, Research Funding: AstraZeneca, Boehringer-Ingelheim, Mirati, Bristol Myer Squibb, Takeda; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer-Ingelheim, Bristol Myer Squibb, Mirati, Spectrum, Takeda Pharmaceuticals; Non-Financial Interests, Personal and Institutional, Steering Committee Member: AstraZeneca – Chairman (AEGEAN). G. Ruiter: Non-Financial Interests, Institutional, Advisory Board: Boehringer Ingelheim; Non-Financial Interests, Institutional, Local PI: AstraZeneca, AbbVie, Daiichi Sankyo, Cullinan Oncology, Boehringer Ingelheim, Merus, Bayer, Navire, BridgeBio, Bristol Myers Squibb, Ikena Oncology, Scorpion Therapeutics, Taiho Oncology, Revolution Medicine, Pierre Fabre. All other authors have declared no conflicts of interest.