Abstract 34P
Background
Beamion LUNG-1 is an ongoing first-in-human Ph Ia/b trial assessing zongertinib in pts with HER2 aberration-positive solid tumours (Ph Ia) and HER2 m+ NSCLC (Ph Ib; NCT04886804). Here, we present updated Ph Ia (29 Sept 2023 cut-off) and interim Ph Ib (31 July 2023 cut-off) data.
Methods
Ph Ia recruited pts with HER2 aberration-positive (gene mutations or rearrangements, amplification or overexpression) advanced solid tumours who were treated with escalating doses of zongertinib BID (≥15 mg) or QD (≥60 mg). Primary endpoint: maximum tolerated dose (MTD). Ph Ib is recruiting patients with HER2 m+ advanced/metastatic NSCLC (Cohorts: 1, pre-treated HER2 TKD m+; 2, treatment [Tx]-naïve HER2 TKD m+; 3, previously treated non-TKD HER2 m+; 4, active brain metastases; 5, prior Tx with anti-HER2 antibody–drug conjugates). The primary endpoint was overall response rate (ORR) by investigator assessment.
Results
Ph 1a: pts (n=61) received zongertinib at 15/30/60/100/150 mg BID (n=3/3/4/4/3) and 60/120/180/240/300/360 mg QD (n=5/4/9/12/10/4). Median duration (range) of Tx: 4.8 (< 1─18.7) mos; ongoing in 35 pts. There were two dose-limiting toxicities during the MTD evaluation period (grade [G] 3 decreased platelets [360 mg QD]; G3 diarrhoea [240 mg QD]); the MTD was not reached for BID or QD. TRAEs (all/G3/G4/G5): 72/10/0/0%. Serious TRAEs: 2% (n=1; G3 AST/ALT). In 53 evaluable pts, ORR/disease control rate (DCR): 49/91%. Median DoR: 12.7 mos (95% CI: 4.2─12.7). In 36 evaluable NSCLC pts, ORR/DCR: 58/97%. As of 31 July 2023, 42 patients had been treated in Cohort 1 of Ph Ib (randomised to 120/240 mg QD). TRAEs (all/G3/G4/G5): 67/5/5/0%, most commonly diarrhoea (G1/G2/G≥3; 24/5/0%) and rash (17/5/0%). Most pts with diarrhoea (64%) had only one occurrence. Serious TRAEs: 5% (n=2; G4 decreased neutrophils, G4 immune thrombocytopenia). No AEs led to Tx discontinuation. ORR/DCR (n=23): 74/91%. All responding patients remained on Tx at data cut-off.
Conclusions
Zongertinib was well tolerated and exhibited promising efficacy in pts with HER2 TKD m+ NSCLC. Prespecified futility analysis was passed. The trial is ongoing.
Clinical trial identification
NCT04886804.
Editorial acknowledgement
Medical writing support for the development of this abstract, under the direction of the authors, was provided by Lynn Pritchard DPhil, CMPP, of Ashfield MedComms, an Inizio Company, and funded by Boehringer Ingelheim.
Legal entity responsible for the study
Boehringer Ingelheim.
Funding
Boehringer Ingelheim.
Disclosure
F. Opdam: Non-Financial Interests, Personal, Principal Investigator: GSK, Int1B3, AstraZeneca, Cytovation, Relay, Taiho, Roche, Merus, Boehringer Ingelheim, Crescendo, Pierre Fabre, Lilly, RevMed, Incyte. M. Barve: Financial Interests, Personal, Full or part-time Employment: Texas Oncology; Financial Interests, Personal, Stocks/Shares: Texas Oncology; Financial Interests, Institutional, Research Grant: Mary Crowley Research Center. H. Tu: Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Eli Lilly, Roche, Pfizer, Boehringer Ingelheim. Y. Wu: Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Takeda; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Lilly, Roche, Pfizer, Boehringer Ingelheim, MSD Oncology, Bristol Myers Squibb, Hengrui Pharmaceutical, BeiGene Beijing; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim, Roche, Pfizer, Bristol Myers Squibb. D. Berz: Financial Interests, Personal, Speaker’s Bureau: Jazz Pharmaceutics, Sun Pharma; Financial Interests, Personal, Full or part-time Employment: Valkyrie Clinical Trials; Financial Interests, Personal, Leadership Role: Jazz Pharmaceutics, Sun Pharma; Financial Interests, Personal, Other, Honoraria: Jazz Pharmaceutics, Sun Pharma; Financial Interests, Personal, Other, Travel/accomodation: Jazz Pharmaceutics; Financial Interests, Institutional, Principal Investigator: Boehringer Ingelheim, Ascendis, BeiGene, BioNTech, BMS, Black Diamond Therapeutics, eFFECTOR, Faeth, G1 Therapeutics, Genprex, Hongyun Biotech, Incyte, Inhibrx, Mirati, Seagen, Summit Therapeutics, WhiteOak, Xencor. M. Rohrbacher: 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 . K. Yoh: Financial Interests, Personal, Invited Speaker: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Janssen, Kyowa Kirin, Lilly, Merck Serono, Novartis, Ono, Otsuka, Taiho, Takeda; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Seagen; Financial Interests, Institutional, Funding: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Lilly, MSD, Pfizer, Taiho, Takeda. N. Yamamoto: Financial Interests, Personal, Other, Honoraria: Chugai Pharmaceutical, Ono Pharmaceutical, Daiichi Sankyo/UCB Japan, Eisai; Financial Interests, Personal, Advisory Role: Eisai, Takeda, Boehringer Ingelheim, Cimic, Chugai Pharmaceutical, Healios, Merck; Financial Interests, Personal, Funding, Research Funding; An Immediate Family Member: Chiome Biosciences, Otsuka; Financial Interests, Institutional, Research Grant, Research Funding: Chugai Pharmaceutical, Taiho Pharmaceutical, Eisai, Astellas Pharma, Novartis, Daiichi Sankyo, Lilly Japan, Boehringer Ingelheim, Takeda, Kyowa Hakko Kirin, Bayer, Pfizer, Ono Pharmaceutical, Janssen, MSD, AbbVie, Bristol Myers Squibb, Merck Serono, GSK, Sumitomo Dainippon, Carna Biosciences, Genmab/Seattle Genetics, Shionogi, Toray Indutries, Kaken Pharmaceutical, AstraZeneca, CMIC, InventisBio, Rakuten Medical. J. Heymach: Financial Interests, Personal, Advisory Board: Genentech, Mirati Therapeutics, Eli Lilly & Co, Janssen Pharmaceuticals, Boehringer Ingelheim Pharmaceuticals, Regeneron, Takeda Pharmaceuticals, BerGenBio, Jazz Pharmaceuticals, Curio Science, Novartis, AstraZeneca Pharmaceuticals, BioAlta, Sanofi, Spectrum Pharmaceuticals, GSK, EMD Serono, BluePrint Medicine, Chugai Pharmaceutical; Financial Interests, Personal, Licensing Fees: Spectrum; Financial Interests, Personal, Royalties: Spectrum; Financial Interests, Personal, Research Grant: AstraZeneca, Boehringer Ingelheim, Spectrum, Mirati, Bristol-Myer Squibb, Takeda.