First-in-human study of ALK201, a FGFR2b-targeting antibody-drug conjugate (ADC) for patients (pts) with advanced solid tumors.

3025 Background: ALK201 is a novel ADC comprising of an anti-FGFR2b humanized monoclonal antibody conjugated to topoisomerase I inhibitor Exatecan via a cleavable and highly hydrophilic linker. ALK201 exhibited potent anti-tumor activities in preclinical studies with a tolerable safety profile. Here we report the preliminary results of ALK201 monotherapy for pts with advanced solid tumors from the first-in-human phase I/II trial (NCT06656390). Methods: This is an ongoing, multicenter, open-label study being conducted in the US, China, and Australia, which consists of two parts, dose-escalation (Part A) and dose-expansion (Part B). The Part A employs the Bayesian optimal interval (BOIN) with backfilling (BF) design to determine the MTD and recommended doses for Part B. In Part A, pts with advanced solid tumors refractory to standard therapies were treated with ALK201 at 1.5-9.6 mg/kg Q3W. Part B was dose expansion at effective doses identified in Part A. The primary endpoint was safety. Secondary endpoints included efficacy and pharmacokinetics (PK). Results: As of December 31, 2025, 38 pts with advanced solid tumors were enrolled in Part A and dosed at 1.5 mg/kg (n=4), 3.0 mg/kg (n=3), 4.8 mg/kg (n=5) ,7.2 mg/kg (n=12), 8.4 mg/kg (n=5) and 9.6 mg/kg (n=9). The median age was 58 years (range 25-74). All pts progressed after receiving a median of 3 prior lines of standard anti-cancer therapy (range 1-8). 28 (73.7%) were Asian and 10 (26.3%) were White. No dose-limiting toxicities (DLTs) have been observed at doses up to 9.6 mg/kg. MTD was not reached. Treatment-related adverse events (TRAEs) occurred in 78.9% pts. The most common TRAEs (incidence ≥10%) were nausea (44.7%), anemia (21.1%), vomiting (21.1%), decreased appetite (13.2%), white blood cell count decreased (13.2%), neutrophil count decreased (10.5%), platelet count decreased (10.5%), AST increased (10.5%), hypoalbuminemia (10.5%) and fatigue (10.5%). Grade ≥3 TRAEs occurred in 23.7% pts and were exclusively reversible hematologic toxicities. Treatment related ocular adverse events limited to grade 1 in 4 pts (10.5%) with minimal clinical impact. Among 25 pts who were evaluable for response, 6 achieved a partial response (PR), 11 achieved stable disease (SD) in best of response. The objective response rate (ORR) and disease control rate (DCR) were 24% (95% CI: 9.4, 45.1) and 68% (95% CI: 46.5, 85.1), respectively. The ORR and DCR in ≥ 7.2mg/kg groups were 35.7% (5/14) and 100% (14/14), respectively. PK analysis showed a dose-dependent ADC and total antibody exposure at doses of 1.5-9.6 mg/kg. ALK201 elimination half-life was approximately 6-11 days. Conclusions: ALK201 demonstrated a favorable safety profile in pts with pretreated advanced solid tumors. Promising anti-cancer activity was observed at doses of 7.2 mg/kg and above, warranting further investigation in those effective dose levels. Clinical trial information: NCT06656390 .