LAUSR

Background: There is an unmet need for effective TKIs against HER2 mutations in solid tumors, particularly in NSCLC. BI 1810631 is a HER2-selective TKI that covalently binds to both wild-type and mutated HER2 receptors, including exon 20 insertions, whilst sparing EGFR signaling. This ongoing Phase Ia/Ib, open-label, non-randomized study aims to determine the safety, MTD, PK, pharmacodynamics and preliminary efficacy of BI 1810631 in pts with HER2 aberration-positive solid tumors (NCT04886804). Here, we present interim results of Phase Ia. Materials and Methods: In Phase Ia, pts with HER2 aberration-positive (overexpression, gene amplification, somatic mutation, or gene rearrangements) 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 30 pts with advanced HER2 tyrosine kinase domain mutation-positive, pre-treated NSCLC. Additional cohorts may be included in the future. Primary endpoints: MTD based on number of DLTs; number of pts with DLTs (Phase Ia); objective response (Phase Ib). Secondary endpoints: number of pts with DLTs throughout entire treatment period and PK parameters (Phase Ia/Ib); duration of response, disease control, duration of disease control, and PFS (Phase Ib). Results: As of 21 December 2022, 34 pts had been treated in the US, The Netherlands, Japan, and China. Pts had NSCLC (n = 21), colorectal cancer (n = 3), or other tumors (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 was 4 (range 1-14). Treatment is ongoing in 23 pts. To date, three DLTs have been observed (grade 2 edema [60 mg BID], grade 3 anemia [60 mg QD], grade 3 elevated ALT [180 mg QD]). The MTD has not been reached with either schedule. Treatment-related adverse events (TRAEs) were reported in 23 pts (68%). The most common TRAEs were diarrhea (n = 9), anemia (n = 5), increased alkaline phosphatase, increased creatinine, increased ALT, hypoalbuminemia (all n = 4), hypocalcemia, elevated AST, dry skin, increased GGT (all n = 3). Three pts had grade 3 TRAEs (anemia/increased 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; esophagus, cholangiocarcinoma: n = 1). The DCR was 90%. In 19 NSCLC pts evaluable for response, the ORR was 42% and the DCR was 95%. Updated data will be presented at the meeting. Conclusions: These preliminary data indicate that BI 1810631 is well tolerated and shows encouraging anti-tumor activity in pts with HER2 aberration-positive solid tumors. Recruitment into Phase Ia is ongoing. Citation Format: John Heymach, Frans Opdam, Minal Barve, Hai-Yan Tu, Yi-Long Wu, Neil Gibson, Behbood Sadrolhefazi, Josep Serra, Kiyotaka Yoh, Noboru Yamamoto. Updated data from the Phase I Beamion Lung 1 trial of the HER2 tyrosine kinase inhibitor (TKI), BI 1810631, as monotherapy in patients (pts) with advanced/metastatic solid tumors with HER2 aberrations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT203.