Phase I study of BC001, a novel fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2, in advanced solid tumors.

Background: BC001 is a novel fully human immunoglobulin G1 monoclonal antibody blocking VEGFR2. This phase I study aimed to assess BC001 alone and plus chemotherapy in solid tumors.
Methods: In dose escalation part, BC001 was assessed at dose levels of 2, 4, 8, 12, 16 mg/kg on day 1,15, every 28 days, followed an accelerated titration and "3 + 3" design. BC001 plus paclitaxel was assessed at dose level of 8, 10 mg/kg. The primary endpoints included the DLT, MTD and RDE of BC001. In dose expansion part, it aimed to assess the anti-tumor activity of BC001 alone and plus chemotherapy in gastric cancer as 2nd line treatment.
Results: Overall, 53 patients were finally enrolled in this study (phase Ia, n = 28; phase Ib, n = 25). In phase Ia part, 1 DLT (grade 4 neutropenia lasting 4 days) was observed in BC001(8 mg/kg) plus paclitaxel cohort. MTD was not reached. All patients experienced TEAEs of any grade. Twenty-four of them suffered ≥ grade 3 TEAEs. leukopenia (n = 33, 62.3%), hemoglobin decreased (n = 32, 60.4%), neutropenia (n = 29, 54.7%) were commonly observed hematological toxicities. The half-life of 140-240 h. And the PK parameters were not largely influenced by combination with paclitaxel. The serum sVEGFR-1, VEGF-A, sVEGFR-2 could not predict the efficacy. Based on the safety, PK and efficacy data, BC001 of 8 mg/kg was determined as RED. Among the GC patients(n = 21) who receiving BC001 plus paclitaxel as 2nd-line treatment in phase 1b part, 6 patients achieved PR and 10 patients experienced SD. The ORR was 28.6% (95% CI 11.3%, 52.2%) and the DCR was 76.2% (95% CI 52.8%, 91.8%), with the median PFS of 5.4 months (95% CI 1.9, 7.0) and OS of 9.4 months (95% CI 5.4, NA). The median DoR was 5.1 months (95% CI 2.6, NA).
Conclusions: BC001 showed acceptable safety profile and preliminary response in both single-agent and combination with chemotherapy cohorts, especially in GC.
(© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)