Phase I study of BL-M05D1, a novel Claudin18.2-directed antibody-drug conjugate (ADC), in patients with locally advanced or metastatic Claudin18.2–expressing solid tumors.

Abstract

3030 Background: BL-M05D1 is a novel Claudin18.2-directed ADC with a potent topoisomerase I inhibitor Ed-04. Results for safety and efficacy data from a phase I study on BL-M05D1 in patients (pts) with locally advanced or metastatic (LA/M) Claudin18.2-expressing solid tumors are presented. Methods: Pts who had LA/M solid tumors enrolled in dose escalation and dose expansion phase, and treated with BL-M05D1 at 0.66, 2.0, 3.0, 4.0 or 5.0mg/kg on Day 1 every 3 weeks (D1 Q3W). Gastric cancer/gastroesophageal junction cancer (GC/GEJ), biliary tract cancer (BTC), and pancreatic cancer (PanC) patients with Claudin18.2-expressing enrolled in dose expansion phase were treated at 2.0, 3.0 or 4.0mg/kg D1 Q3W. Results: As of Nov 30, 2025, a total of 245 pts were enrolled (87 GC/GEJ, 53 BTC, 104 PanC) and 1 other). The most frequent grade≥3 TRAEs were all hematological, including thrombocytopenia (33.9%), neutropenia (32.7%), leukopenia (31.8%) and anemia (14.3%); non-hematologic TRAEs were relatively low. One pt at 5.0mg/kg group experienced grade 3 febrile neutropenia as a DLT. No treatment-related deaths or ILD were reported. In PanC, BL-M05D1 has demonstrated a promising efficacy with an ORR of 35.7% and mPFS of 5.6 mo at 4.0mg/kg in CLDN18.2-positive pts; in the second line pts, ORR was 50.0% with a mPFS of 5.7 mo. Furthermore, BL-M05D1 has shown promising efficacies in CLDN18.2-positive GC and BTC with an ORR of 39.2% and 37.9%, and mPFS of 5.4 mo and 5.9 mo, respectively, at 4.0mg/kg. Efficacy results are summarized below. Conclusions: BL-M05D1 has demonstrated a promising antitumor activity with a tolerable safety profile in pts with pretreated Claudin18.2-positive PanC, GC, and BTC. 4.0mg/kg D1 Q3W was chosen as RP2D. The data support further development of BL-M05D1 in Claudin18.2-positive PanC, GC, and BTC. Phase III studies are in preparation. Clinical trial information: NCT06349811 . PanC-Total * PanC CLDN 18.2 + # 4.0 mg/kg PanC CLDN 18.2 + # 1 Prior Chemo in 4.0mg/kg GC-Total * GC CLDN 18.2 + # 4.0 mg/kg GC CLDN 18.2 + # 1 Prior Chemo in 4.0 mg/kg BTC-Total * BTC CLDN 18.2 + # 4.0 mg/kg BTC CLDN 18.2 + # 1 Prior Chemo in 4.0 mg/kg N = 81 N = 28 N = 16 N = 79 N = 51 N = 29 N = 40 N = 29 N = 20 Median prior LoT (range) 2 (1-4) 2 (1- 3) / 2 (1-4) 1 (1-3) / 1 (1-3) 1 (1-3) / ORR, % (95% CI) 17.3 (9.8-27.3) 35.7 (18.6-55.9) 50.0 (24.7-75.3) 35.4 (25.0-47.0) 39.2 (25.8-53.9) 44.8 (26.4-64.3) 37.5 (22.7-54.2) 37.9 (20.7-57.7) 45.0 (23.1-68.5) DCR, % (95% CI) 74.1 (63.1-83.2) 89.3 (71.8-97.7) 100 (79.4-100) 88.6 (79.5-94.7) 88.2 (76.1-95.6) 86.2 (68.3-96.1) 92.5 (79.6-98.4) 93.1 (77.2-99.2) 90.0 (68.3-98.8) mFU for PFS (mo) 2.8 5.5 4.2 4.4 4.4 4.3 2.8 2.7 2.7 mPFS (mo) 4.0 5.6 5.7 4.4 5.4 7.7 6.9 5.9 5.9 * Efficacy analysis included all pts who received at least one dose of BL-M05D1 and with at least one post baseline scan. # PanC CLDN 18.2 +: IHC 2+/3+ ≥ 50%; GC CLDN 18.2 +: IHC 2+/3+ ≥ 40%; BTC CLDN 18.2 +: IHC1+/2+/3+≥30%.