Abstract CT185: A phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of BC3402 in advanced solid malignancies

Abstract Background: BC3402, an IgG4 monoclonal antibody (mAb) that targets TIM-3, is being developed for solid and hematological malignancies. In preclinical studies in immunocompetent cancers, BC3402 demonstrated synergy when combined with mAbs to PD-1 and/or CTLA-4, supporting a rationale for combination strategies in the clinic. As a first step, the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary anti-tumor activity of BC3402 monotherapy was evaluated in patients (pts) with advanced solid malignancies. Methods: In this phase I, open-label study, multiple doses of BC3402 were explored in pts with advanced solid cancers who had been previously treated with standard therapies to evaluate its safety and tolerability and recommend doses for further development. An accelerated titration design was used to select doses in the first two dose levels (0. 02 and 0. 2mg/kg IV Q3W) followed by a standard “3+3” design in the remainder of the study (1, 5, 10, 20 and 30 mg/kg IV Q3W). Results: Nineteen pts (median range age: 59 29-73; 63. 2% male; 94. 7% ECOG 1) were treated with at least one 3-week cycle of BC3402. DLT was not observed, and adverse events (AEs) were not dose related. The most common TEAEs (incidence ≥20%) and TRAEs (incidence ≥10%) were grade 1-2. The most common (incidence ≥10%) TEAE ≥ grade 3 was dysphagia (2/19 pts, 10. 5%), which occurred in the 5 mg/kg and 10 mg/kg dose cohorts. Two pts reported grade 3 or above TRAEs – grade 3 hypertension (5 mg/kg) and grade 3 gamma-glutamyl transferase increase (10 mg/kg), There were neither dose interruptions nor treatment discontinuation due to AEs. There were no objective responses. Seven of 18 pts who were evaluable for tumor assessment had stable disease as best response with one pt (20 mg/kg dose cohort) with NSCLC having sustained reductions (32 weeks) in target lesions. Median Tmax values ranged from 1. 08 to 2. 96 hours, and mean T1/2 values ranged from 119 to 182 hours at doses ranging from 5-30 mg/kg. Exposure was linear in the dose range of 1 -30 mg/kg, and there was no drug accumulation after the second cycle. Receptor occupancy saturation was observed within the tested dose range. Based on these data, the RP2D was determined as 20mg/kg every 2 weeks or 30mg/kg every 3 weeks. Conclusions: BC3402 exhibited favorable safety profile and PK characteristics when administered as single infusion at doses ranging from 0. 02 mg/kg to 30 mg/kg Q3W in pts with advanced solid cancers, and its safety profile supports further disease-directed studies in combination with other immune checkpoint inhibitors and/or rational therapeutic modalities. Citation Format: Yi-Long Wu, Huajun Chen, Sheng Wang, Rui Zhang, En-Tzu Tang, Weiwei Zhang, Kaicun Gu, Yiwei Wang, Yongjiang Hei. A phase I clinical trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumor activity of BC3402 in advanced solid malignancies abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84 (7Suppl): Abstract nr CT185.