Abstract 633P
Background
Zongertinib is a novel, HER2-selective tyrosine kinase inhibitor that spares EGFR. Beamion LUNG-1 (NCT04886804) is a first-in-human Phase (Ph) Ia/Ib trial designed to evaluate the safety and efficacy of zongertinib in patients (pts) with HER2-driven solid tumors (Ph Ia) and pretreated HER2 mutation-positive NSCLC (Ph Ib). Here, we focus on Asian pts in Ph Ia.
Methods
Pts with confirmed HER2 aberration-positive unresectable/advanced/metastatic solid tumors received zongertinib twice daily (BID; ≥15 mg) or once daily (QD; ≥60 mg) in 3-week cycles. Dose escalation was guided by a Bayesian model with overdose control. Treatment (Tx) continued until undue toxicity or withdrawal of consent. The primary endpoint was MTD, based on the number of DLTs during the MTD evaluation period.
Results
As of May 23, 2024, 105 pts had received zongertinib in Ph Ia; of these, 51 were recruited in Asia (44 Japan; 7 China). Overall, most (54, 51%) pts had NSCLC; 57 pts (54%) had a HER2 mutation. Overall median Tx duration was 4.2 months (range 0–28); 47 pts remained on Tx at data cut-off. Two DLTs were seen during the MTD evaluation period: G3 decreased platelet count (360 mg QD) and G3 diarrhea (240 mg QD). MTD was not reached for BID or QD schedules. In all pts, treatment-related adverse event (TRAE) frequencies (all/G3/G4/G5, %) were 82/10/1/0; 3 pts had serious TRAEs. The most common TRAEs (all/G3, %) were diarrhea (51/1), rash (16/2), anemia (10/0), increased ALT (10/4) and decreased appetite (10/1). 3 pts discontinued due to AEs (any cause). In Asian pts, TRAE frequencies (all/G3/G4/G5, %) were 81/8/0/0; there were no serious TRAEs. The most common TRAEs (all/G3, %) were diarrhea (55/0), anemia (16/0), dry skin (10/0), rash (10/0) and stomatitis (10/0). One pt discontinued Tx due to a TRAE (G3 increased ALT). In all response-evaluable pts (n=99) the confirmed ORR/DCR were 32/88%; median DoR was 12.7 mos. In 47 evaluable Asian pts, confirmed ORR/DCR were 34/94%; 8/16 responding pts remained on Tx.
Conclusions
Zongertinib was well tolerated and demonstrated promising efficacy in pts with HER2-driven solid tumors. Safety and efficacy in Asian pts were similar to the overall population, with no unexpected safety signals.
Clinical trial identification
NCT04886804 May 12, 2021.
Editorial acknowledgement
Medical writing support for the development of this abstract, under the direction of the authors, was provided by Ellie Sherwood of Ashfield MedComms, an Inizio Company, and funded by Boehringer Ingelheim.
Legal entity responsible for the study
Boehringer Ingelheim.
Funding
Boehringer Ingelheim.
Disclosure
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. F. Opdam: Financial Interests, Institutional, Other: AstraZeneca, Boehringer Ingelheim, Cytovation, GSK, InteRNA, Merck, Merus NV, Pierre Fabre, Taiho Oncology. M. Barve: Financial Interests, Personal, Research Grant: Mary Crowley Research Center; Financial Interests, Personal, Speaker, Consultant, Advisor: I-Mab Therapeutics, Tempus; Financial Interests, Personal, Stocks/Shares: Texas Oncology. H. Tu: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Roche, Pfizer. Y. Wu: Non-Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, Boehringer Ingelheim, Pfizer, Roche; Financial Interests, Personal, Speaker, Consultant, Advisor: AstraZeneca, BeiGene Beijing, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, Hengrui Pharmaceutical, MSD Oncology, Pfizer, Roche. D. Berz: Financial Interests, Personal, Full or part-time Employment: Valkyrie Clinical Trials; Financial Interests, Personal, Leadership Role: Jazz Pharmaceuticals, Sun Pharma; Financial Interests, Personal, Other, Honoraria: Jazz Pharmaceuticals, Sun Pharma, EMD; Financial Interests, Personal, Other, Travel and accommodation: Jazz Pharmaceutics, EMD; Financial Interests, Institutional, Principal Investigator: Ascendis, Boehringer Ingelheim, Beigene, BioNTech, Black Diamond Therapeutics, BMS, eFFECTOR, Faeth, G1 Therapeutics, Genprex, Hongyun Biotech, Incyte, Inhibrx, Mirati, Seagen, Summit Therapeutics, WhiteOak, Xencor; Financial Interests, Personal, Speaker’s Bureau: Jazz Pharmaceuticals, Sun Pharma, EMD. L. Schroeter: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. B. Sadrolhefazi: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim. J. Serra: 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 Lily & Co, EMD Serono, Genentech, GSK, IDEOlogy Health, Immunocore, InterVenn Biosciences, Janssen Biotech, Janssen Pharmaceuticals, Mirati Therapeutics, Moffitt Cancer Center, ModeX, Nexus Health Systems, Novartis Pharmaceuticals, OncoCyte, RefleXion, Regeneron Pharmaceuticals, Roche, Sandoz Pharmaceutical, Sanofi, Spectrum Pharmaceuticals, Takeda, uniQure; 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: Spectrum, AstraZeneca, Boehringer Ingelheim, Mirati, Bristol-Myer Squibb, Takeda; Non-Financial Interests, Personal and Institutional, Steering Committee Member: AstraZeneca – Chairman (AEGEAN). 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.