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

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). 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). 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. 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.