TAVO412, an Anti-EGFR, cMET and VEGF Trispecific Antibody: Initial Results from a Phase I Dose Escalation Study in Patients with Advanced Solid Tumors

PURPOSE: We report the results of a Phase 1 study of TAVO412, an anti-EGFR, cMET, and VEGF-A multi-specific antibody. PATIENTS AND METHODS: Patients of age ≥18 years with advanced solid tumors refractory to standard therapies were enrolled (TAVO412-CN001, NCT06761651). The study used a standard 3 + 3 design for dose-escalation from 150 to 1500 mg every two weeks in a 28-day cycle. Patients were backfilled for further assessment of safety and preliminary anti-tumor activities. RESULTS: The study included 67 patients, with 6 tumor types. Serum drug exposures increased with the dose. TAVO412 had low immunogenicity (5.9%). No DLTs were reported and the MTD was not reached up to 1500 mg. The most common treatment-related (TR) AEs (≥30%) across all doses were rash, hypoalbuminemia, stomatitis, infusion related reaction, increased ALT, and hypokalemia. Preliminary anti-tumor activities were observed in NSCLC patients (n = 27) with 5 PRs (3 of 9 EGFR Exon20ins and 2 of 12 Exon21 L858R) and 13 SDs, in ESCC (n = 11) with 1 PR and 8 SDs, and in CRC (n = 15) with 4 PRs and 7 SDs, in the dose range from 750 to 1500 mg. All PRs were confirmed except 1. The longest treatment duration was approximately 39 weeks. Baseline soluble VEGF-A levels correlated with treatment responses. CONCLUSIONS: TAVO412 was tolerated up to 1500 mg, with mostly target-related AEs. Preliminary activities of TAVO412 were observed in CRC, ESCC, and NSCLC patients who had been heavily treated. Further evaluation of TAVO412 in patients with these tumor types is warranted.