CELL INTELLIGENCE · 肿瘤细胞治疗研究

B-cell maturation antigen (BCMA) is an ideal target in multiple myeloma (MM) due to highly specific expression in malignant plasma cells. BCMA-directed therapies including antibody drug conjugates, chimeric antigen receptor-T cells and bispecific antibodies (BsAbs) have shown high response rates in MM. WVT078 is an anti-BCMA× anti-CD3 BsAb that binds to BCMA with subnanomolar-affinity. It was selected based on potent T cell activation and anti-MM activity in preclinical models with favorable tolerability in cynomolgus monkey. In the ongoing first-in-human phase I dose-escalation study (NCT04123418), 33 patients received intravenous WVT078 once weekly at escalated dosing.

At the active doses of 48-250 µg/kg tested to date (n = 26), the overall response rate (ORR) was 38. 5% (90% CI: 22. 6-56. 4%) and the complete response rate (CRR, stringent complete response + complete response) was 11. 5%, (90% CI: 3. 2-27. 2%). At the highest dose level tested, the ORR was 75% (3 of 4 patients).

26 (78. 8%) patients reported at least one Grade ≥3 AE and 16 of these AEs were suspected to be drug related. 20 patients (60. 6%) experienced cytokine release syndrome. WVT078 has an acceptable safety profile and shows preliminary evidence of clinical activity at doses tested to date.