Abstract P4-01-07: FS-1502, an anti-HER2 ADC, in Patients with HER2-Expressing Advanced Solid Tumors: A Phase 1a Dose-Escalation Study

Abstract Background: FS-1502 is a HER2-targeting antibody drug-conjugate with a cleavable β-glucuronide linker and an antimitotic agent (monomethyl auristatin F) which showed promising antitumor activity in preclinical studies. We are evaluating the safety and tolerability of FS-1502 in patients with HER2-expressing advanced solid tumors (NCT03944499). Methods: Patients with HER2-expresssing advanced solid tumors who had failed prior standard of care therapies were enrolled in a single-arm, open-label, dose-escalation phase Ia study in China. FS-1502 was given IV once in 21-day or 28-day cycles. The primary endpoint was incidence of dose-limiting toxicity (DLT). Adverse events (AEs), objective response rate (ORR) and duration of response (DoR) were also assessed. Data cutoff was December 30, 2021. Results: A total of 67 patients, 64 with breast cancer and 3 with other solid tumors, with median 3 prior therapies (range 1-10), were enrolled in 5 sites and treated with FS-1502 at doses of 0.1-3.5 mg/kg. Two DLTs, as defined by the protocol, were observed, with one G2 decrease in creatinine clearance at 3.0 mg/kg and one G3 thrombocytopenia with hemorrhage at 3.5 mg/kg. No Grade 4/5 events were observed. Grade 3 TRAEs were observed in 24 (35.8%) patients with the most common AEs of hypokalemia (14.9%) and decreased platelet count (9.0%). ORRs were observed at doses at or above 1.0 mg/kg with an ORR of 66.7% (4/6) at the recommended phase 2 dose (RP2D) of 2.3 mg/kg. Median duration of response (DoR) across all dose levels was 9.2 months (95%CI 5.6-NR). ORR for HER2-low patients was 42.9% (3/7). Plasma concentration and exposure (AUC) based on total ADC and total antibody increased dose proportionally at ≥1.0 mg/kg, with a T1/2 of 2.4-4.9 days. The incidence and magnitude of immunogenicity were low. While no MTD was determined, the 2.3mg/kg dose once in a 21-day cycle was selected as the RP2D based on safety, antitumor activity and PK data. Conclusions: FS-1502 was well-tolerated and demonstrated encouraging antitumor activity in both HER2-high and -low patients. Phase Ib and phase II clinical trials with FS-1502 are currently ongoing in various solid tumor indications including breast, gastric, and colorectal cancer. Citation Format: Qiao Li, Xian Wang, Ying Cheng, Yunjiang Liu, Jianhua Chang, Zhuo Wang, Chunjiao Wu, Mingxia Wang, Ai-Min Hui, Zhuli Wu, Yongli Jin, Xin Huang, Liping Zhong, Lei Diao, Han Zhao, Binghe Xu. FS-1502, an anti-HER2 ADC, in Patients with HER2-Expressing Advanced Solid Tumors: A Phase 1a Dose-Escalation Study [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-01-07.