A randomized Phase 1 study of telisotuzumab adizutecan (ABBV-400, Temab-A) in combination with bevacizumab versus trifluridine-tipiracil with bevacizumab in patients with metastatic colorectal cancer.
Abstract
Background
Telisotuzumab adizutecan (ABBV-400, Temab-A) is an antibody-drug conjugate targeting c-Met (MET) protein with adizutecan, a novel topoisomerase 1 inhibitor payload. In monotherapy dose escalation, Temab-A demonstrated a manageable safety profile and promising antitumor activity in advanced colorectal cancer (CRC; NCT05029882). Based on these results, a randomized cohort of Temab-A + bevacizumab (Bev) versus trifluridine-tipiracil (FTD-TPI) + Bev (standard-of-care) was added with the hypothesis that addition of Bev would enhance efficacy. PATIENTS AND
Methods
Patients unselected for c-Met protein expression with advanced CRC were enrolled in 2 parts. In dose escalation, patients received Temab-A 1.6, 2.0, or 2.4 mg/kg + Bev 7.5 mg/kg Q3W. In dose optimization, patients were randomized 1:1:1 to Temab-A 2.0 or 2.4 mg/kg + Bev 7.5 mg/kg Q3W, or FTD-TPI 35 mg/m2 Days 1-5 and 8-12 Q4W + Bev 5.0 mg/kg Q2W. Primary objectives were safety, pharmacokinetics, and efficacy of Temab-A + Bev.
Results
Overall, 83 patients received treatment with Temab-A + Bev (n=63) or FTD-TPI + Bev (n=20) with median 3 (range, 1-8) prior lines of treatment and median follow-up of 18.2 months. Treatment-related adverse events were primarily gastrointestinal and hematological with low discontinuation rates (Temab-A 2.0: 3/26 [12%]; Temab-A 2.4: 1/30 [3%]). Objective response rate was 19% and 30% with Temab-A 2.0 and 2.4 + Bev, respectively, and 0% with FTD-TPI + Bev. For Temab-A 2.0 and 2.4 + Bev vs FTD-TPI + Bev, median progression-free survival was 5.6 and 6.8 months vs 4.2 months; median overall survival was 11.2 (HR=0.75) and 14.7 months (HR=0.62) vs 10.2 months, respectively.
Conclusion
Temab-A 2.4 mg/kg + Bev demonstrated the most favorable risk-benefit profile, was tolerable, and had clinically meaningful improvements in efficacy versus FTD-TPI + Bev for advanced CRC. The regimen is being evaluated in the global randomized Phase 3 trial AndroMETa-560 (NCT07525206).