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

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Clinical trial identification

NCT04146610.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

CSPC Zhongqi Pharmaceutical Technology Co., Ltd.

Disclosure

S. Xiang, X. Zhang, S. Wu, M. Li: Financial Interests, Personal, Full or part-time Employment: CSPC Zhongqi Pharmaceutical Technology Co., Ltd.. All other authors have declared no conflicts of interest.