385MO A multicenter, open-label, dose escalation and expansion study of DP303c in patients with HER2-positive pre-treated advanced solid tumors

DP303c is a HER2-targeting ADC with a cleavable linker-MMAE payload. Pre-clinical study demonstrated similar to or better antitumor activity than T-DM1 in xenograft models. Here we present the safety and efficacy of DP303c in patients (pts) with HER2-positive pre-treated advanced solid tumors. Adult pts with HER2-positive advanced solid tumors who were not eligible to receive standard of care (SoC) or had no SoC, or failed SoC were recruited. This phase Ⅰ study consisted of dose escalation with a modified 3+3 design at DP303c 0.5, 1.0, 2.0, 3.0 and 4.0 mg/kg, and then dose expansion at 3.0 mg/kg, intravenously administered every 3 weeks. The primary endpoints were safety and RP2D. As of 28 Feb 2023, 94 pts were enrolled in dose escalation (22 pts) and dose expansion (72 pts). The median follow-up was 11.98 months (mo). Median age was 51.5 yrs (range: 28-73). Tumor types were breast cancer (BC, 68 pts), colorectal cancer (10 pts), gastric cancer (9 pts) and others (7 pts). ECOG PS was 0 in 15 pts (16.0%), and 1 in 79 pts (84.0%). All 94 pts received ≥ 1 prior line of systemic therapy. 65 pts (95.6%) with BC received ≥ 2 prior lines of systemic therapy. One dose limiting toxicity [Grade (G) 3 eye pain] was observed in 4.0 mg/kg with 3.0 mg/kg selected as expansion dose. Treatment-related adverse events (TRAEs) of any grade occurred in all 94 pts, in which 34 (36.2%) were G ≥ 3. The most common G ≥ 3 TRAEs were vison blurred (16.0%), xerophthalmia (6.4%), and neuropathy peripheral (3.2%). No treatment-related death occurred. Among 91 efficacy evaluable pts, ORR and DCR were 42.9% (95%CI: 32.5-53.7) and 68.1% (95%CI: 57.5-77.5). The median PFS and DoR were 4.44 mo (95%CI: 3.35-6.44) and 10.97 mo (95%CI: 3.98-NA) for all 94 pts. The minimal effective dose was 1.0 mg/kg in BC. Among 66 efficacy evaluable pts with BC, ORR and DCR were 51.5% (95%CI: 38.9-64.0) and 77.3% (95%CI: 65.3-86.7). The median PFS and DoR were 6.44 mo (95%CI: 4.14-8.51) and 10.97 mo (95%CI: 3.98-NA) for all 68 pts with BC. DP303c demonstrated promising anti-tumor activity with acceptable safety in pts with pre-treated advanced solid tumors, especially BC. The pivotal phase II study in pts with BC is ongoing.