CLDN18.2–targeting antibody-drug conjugate BA1301 in advanced solid tumors: Results from a phase I clinical trial.

Abstract

4031 Background: Aberrant expression of claudin18.2 (CLDN18.2) has frequently been observed in various solid tumors, making it a promising therapeutic target for those aggressive cancers. BA1301 is an ADC consisting of a fully humanized anti-CLDN18.2 monoclonal antibody conjugated to monomethyl auristatin E, a potent cytotoxic agent via site-specific glycol conjugation and a cleavable linker with a drug-to-antibody ratio of 4. Here we reported the results from a phase 1 dose escalation and dose expansion study of BA1301. Methods: Eligible pts failed or intolerant to standard therapy were enrolled. BA1301 was intravenously administered with accelerated titration (0.1/0.4 mg/kg Q3W) and traditional 3+3 design (1.2/2.0/2.5/3.0mg/kg Q3W). Dose expansion was evaluated at 1.6/2.0/2.5mg/kg Q3W. CLDN18.2 was test by immunohistochemistry [IHC] Claudin18.2 (EPR19202-244) Assay developed by Medx. Moderate to high expression of CLDN18.2 defined as IHC membrane staining intensity ≥2 in ≥40% of tumor cells. Endpoints were safety and efficacy per RECIST v1.1. Results: As of Dec 22, 2025, a total of 91 patients with advanced cancers (gastric cancer [59, 64.8%], biliary tract cancer [14, 15.4%], pancreatic cancer [11, 12.1%], gynecologic cancers [3, 3.3%] and other 4 tumor types) were enrolled, 49 (53.8%) patients had received ≥2 systemic therapies (median 2, range 1-7). In dose escalation (n = 24), No DLTs were observed.80 (87.9%) patients had at least one treatment-related adverse events (TRAEs), and 33 (36.3%) had grade 3 or 4 TRAEs. The most common TRAEs were corneal disorder (51, 56.0%) and anemia (30, 33.0%). 3(3.3%) pts discontinued treatment due to TRAEs, and no treatment related death reported. Among patients with CLDN18.2 moderate to high expression (N=76), 69 at the ≥1.6 mg/kg dose level had at least one post-baseline tumor assessment. Key efficacy outcomes are presented (Table). Conclusions: BA1301 was well-tolerated with a manageable safety profile and demonstrated promising anti-tumor activity in patients with CLDN18.2 moderate to high expression. The findings support further development of BA1301 as a new therapeutic approach to treat CLDN18.2-positive solid tumors. The trial (NCT06927349) is ongoing in China. Clinical trial information: NCT06927349 . Cancer Type ORR n (%) [95%CI] DCR n (%) [95%CI] Gastric cancer (N=49) 14 (28.6）[16.6, 43.3] 35 (71.4) [56.7, 83.4] Biliary tract cancer (N=10) 3 (30.0) [6.7, 65.2] 6 (60.0) [26.2, 87.8] Pancreatic cancer (N=7) 1 (14.3) [0.4, 57.9] 5 (71.4) [29.0, 96.3] Gynecologic cancer (N=3) 1 (33.3）[0.8, 90.6] 3 (100.0) [29.2, 100.0] In total (N=69) 19 (27.5) [17.5, 39.6] 49 (71.0) [58.8, 81.3]