Abstract 40P
Background
This ongoing phase Ia/Ib trial determines the safety, MTD, PK, PD and preliminary efficacy of BI 1810631 in pts with HER2 aberration-positive solid tumours.
Methods
Phase Ia: Pts with HER2 aberration-positive (overexpression, gene amplification/rearrangements or somatic mutation) advanced/unresectable/metastatic solid tumours refractory/unsuitable for standard therapy were enrolled. Pts received escalating doses of BI 1810631 BID (starting dose 15 mg) or BI 1810631 QD (starting dose 60 mg). Phase Ib will initially include 30 pts with advanced HER2 TK domain mutation-positive, pre-treated NSCLC. Primary endpoints: MTD based on number of DLTs; number of pts with DLTs (phase Ia); ORR (phase Ib). Secondary endpoints: number of pts with DLTs throughout entire treatment period and PK parameters (phase Ia/Ib); DoR, DCR, duration of disease control and PFS (phase Ib).
Results
As of 21 Dec 2022, 34 pts have been treated in the US, Netherlands, Japan and China. Pts had NSCLC (n = 21), colorectal cancer (n = 3), or other tumours (n = 10). Most pts had a pathological HER2 mutation (n = 25). Pts received BI 1810631 15, 30, 60, 100, 150 mg BID (n = 3/3/4/4/3) or 60, 120, 180, 240 mg QD (n = 5/4/5/3). Median number of cycles: 4 (range 1–14). Treatment ongoing: n = 23. To date, 3 DLTs has been observed (grade [G] 2 oedema [60 mg BID]; G3 anaemia [60 mg QD]; G3 elevated ALT [180 mg QD]). The MTD has not been reached with either schedule. Treatment-related adverse events (TRAEs) reported in 23 pts (68%). The most common TRAEs were diarrhoea (n = 9), anaemia (n = 5), increased alkaline phosphatase, increased ALT and hypoalbuminemia (all n = 4). Three pts had G3 TRAEs (anaemia/elevated GGT [n = 1]; increased ALT [n = 2]). In 29 pts evaluable for response the ORR (regardless of confirmation) was 34% (n = 10, all PRs; NSCLC: n = 8; oesophagus, cholangiocarcinoma: n = 1). The DCR was 90%. In 19 evaluable NSCLC pts the ORR was 42% and the DCR was 95%. Updated data will be presented at the meeting.
Conclusions
Preliminary data indicate that BI 1810631 is well tolerated and shows encouraging anti-tumour activity in pts with HER2 aberration-positive solid tumours. Phase Ia recruitment is ongoing.
Clinical trial identification
NCT04886804. Release date 14th May 2021.
Editorial acknowledgement
Medical writing support for the development of this poster, under the direction of the authors, was provided by Lynn Pritchard, 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, Institutional, Other, Uncompensated Relationship: Boehringer Ingelheim, AstraZeneca/Merck, GlaxoSmithKline, Cytovation, InteRNA, Merus NV, Taiho Oncology, Pierre Fabre, Incyte. J. Heymach: Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol-Myers Squibb, Spectrum Pharmaceuticals, Guardant Health, Hengrui Pharmaceutical, GlaxoSmithKline, EMD Serono, Takeda, Sanofi/Aventis, Genentech/Roche, Boehringer Ingelheim, Mirati Therapeutics, Janssen, Nexus Health Systems, Pneuma Respiratory; Financial Interests, Institutional, Advisory Role: Eli Lilly; Financial Interests, Personal, Speaker's Bureau: MJH Life Sciences; Financial Interests, Personal, Royalties, Licensing agreement between Spectrum and MD Anderson (including myself) regarding intellectual property for treatment of EGFR and HER2 exon 20 mutations: Licensing agreement between Spectrum and MD Anderson (including myself) regarding intellectual property for treatment of EGFR and HER2 exon 20 mutations; Financial Interests, Personal, Stocks/Shares: Cardinal Spine, Bio-Tree; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Spectrum Pharmaceuticals, GlaxoSmithKline. M. Barve: Financial Interests, Personal, Full or part-time Employment: Texas Oncology Physician Associates; Financial Interests, Personal, Stocks/Shares: Texas Oncology Physician Associates; Financial Interests, Personal, Research Grant: Mary Crowley Cancer Research. H. Tu: Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Eli Lilly, Roche, Pfizer, Boehringer Ingelheim. Y. Wu: Financial Interests, Personal, Other, Honoraria: AstraZeneca, Roche, Boehringer Ingelheim, Takeda, AstraZeneca, Eli 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. N.J. Gibson: 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, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Chugai Pharma, AstraZeneca, Eli Lilly Japan, Kirin Pharmaceuticals, Bristol-Myers Squibb Japan, Taiho Pharmaceutical, Janssen, Daiichi Sankyo/UCB Japan, Boehringer Ingelheim, Novartis; Financial Interests, Institutional, Research Grant: Eli Lilly Japan, AstraZeneca, Pfizer, Taiho Pharmaceutical, Chugai Pharma, MSD, Takeda, Daiichi Sankyo, AbbVie. N. Yamamoto: Financial Interests, Personal, Speaker's Bureau: ONO, Chugai, Daiichi-Sankyo, Eisai; Financial Interests, Institutional, Research Grant: Astellas, Chugai, Eisai, Taiho, BMS, Pfizer, Novartis, Eli Lilly, AbbVie, Daiichi-Sankyo, Bayer, Boehringer Ingelheim, Kyowa Kirin, Takeda, ONO, Janssen Pharma, MSD, Merck, GSK, Sumitomo Pharma, Chiome Bioscience, Otsuka, Carna Biosciences, Genmab, Shionogi, TORAY, KAKEN, AstraZeneca, Cmic; Financial Interests, Personal, Advisory Role: Eisai, Takeda, Otsuka, Boehringer Ingelheim, Cmic, Chugai, Merck, Healios.