1375P - Beamion Lung 1, an ongoing phase Ia/Ib trial of the HER2 TKI, BI 1810631 in patients (pts) with advanced solid tumors with HER2 aberrations: Latest data

Background

The ongoing phase Ia/Ib trial determines the safety, MTD, PK, PD and preliminary efficacy of BI 1810631 in pts with HER2 aberration-positive solid tumors (NCT04886804).

Methods

Phase Ia: pts with HER2 aberration-positive advanced/unresectable/metastatic solid tumors 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 pts with advanced/metastatic HER2 TK domain mutation-positive, pre-treated NSCLC. Additional cohorts may be included. Primary endpoints: MTD based on number of pts with DLTs (phase Ia); ORR (phase Ib). Secondary endpoints: number of pts with DLTs throughout entire treatment (Tx) period and PK parameters (phase Ia/Ib); DoR, DCR, duration of disease control and PFS (phase Ib).

Results

As of 9 Mar 2023, 43 pts had been treated. Pts had NSCLC (n = 27), lung cancer (unspecified; n = 5), colorectal cancer (n = 3), or other tumors (n = 8). Most pts had a pathological HER2 mutation. Pts received BI 1810631 at 15, 30, 60, 100, 150 mg BID (n = 3/3/4/4/3) or 60, 120, 180, 240, 300 mg QD (n = 5/4/6/6/5). Median number of cycles was 4 (range 1–15). Tx is ongoing in 26 pts. To date, 4 DLTs have been observed (grade [G] 2 edema [60 mg BID], G2 diarrhea [150 mg BID], G3 anemia [60 mg QD], G3 increased ALT [180 mg QD]). The MTD has not been reached with either schedule. Tx-related adverse events (TRAEs) were reported in 28 pts (65%; BID/QD 76/58%). The most common TRAEs were diarrhea (33%; BID/QD 47/23%), increased ALT (9%; BID/QD 6/12%) and increased AST (9%; BID/QD 6/12%). Four pts (BID/QD 1/3) had grade 3 TRAEs (increased ALT [n = 3]; increased AST [n = 1]). Of 24 evaluable lung cancer patients (17 are still on Tx), 11 responded (all PRs) and 12 had SD. Two patients with other tumors (esophagus; cholangiocarcinoma) also achieved PR.

Conclusions

These preliminary data indicate that BI 1810631 is well tolerated and shows strong efficacy signals across all dose levels in pts with pretreated HER2 aberration-positive solid tumors. Recruitment into phase Ib is ongoing with the QD regimen. Updated phase 1a data, and emerging Phase1b data, will be presented.

Clinical trial identification

NCT04886804.

Editorial acknowledgement

Medical writing assistance, funded by Boehringer Ingelheim, was provided by Lynn Pritchard, DPhil, of Ashfield MedComms, an Inizio Company, during the preparation of this abstract.

Legal entity responsible for the study

Boehringer Ingelheim.

Funding

Boehringer Ingelheim.

Disclosure

F. Opdam: Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca, Boehringer Ingelheim, Crescendo, Cytovation, GSK, Incyte, IntlB3, Lilly, Merus, Pierre Fabre, Relay, RevMed, Roche, Taiho. J. Heymach: Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, Spectrum, Mirati, Bristol Myers Squibb, Takeda; Financial Interests, Personal, Licencing Fees: Spectrum; 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. Y. Wu: Financial Interests, Personal, Invited Speaker: AstraZeneca, Beigen, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly and Company, Merck Sharp & Dohme, Pfizer, Roche, Sanofi; Financial Interests, Institutional, Research Grant: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Hengrui, Roche; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Hengrui, Roche. L. Schroeter: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim Pharma GmbH & Co. KG. B. Sadrolhefazi: Financial Interests, Personal, Full or part-time Employment: Boehringer Ingelheim Pharmaceuticals, Inc.; Financial Interests, Personal, Sponsor/Funding: Boehringer Ingelheim Pharmaceuticals, Inc. J. Serra: Financial Interests, Personal, Full or part-time Employment: Full or part-time employment Boehringer Ingelheim Financial interests. K. Yoh: Financial Interests, Personal, Invited Speaker: AstraZeneca, Bristol Myers Squibb, Chugai, Daiichi Sankyo, Lilly, Boehringer Ingelheim, Amgen, Takeda; Financial Interests, Institutional, Local PI: AstraZeneca, Lilly, Daiichi Sankyo, AbbVie, Taiho, MSD, Takeda, Amgen, Boehringer Ingelheim, Chugai; Financial Interests, Personal, Steering Committee Member: AstraZeneca. N. Yamamoto: Financial Interests, Personal, Advisory Board: Eisai, Takeda, Boehringer Ingelheim, CMIC, Chugai, Merck, Healios; Financial Interests, Personal, Speaker’s Bureau: Ono, Chugai, Daiichi Sankyo, Eisai; Financial Interests, Personal, Research Funding: 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, Rakuten Medical. All other authors have declared no conflicts of interest.