Dr Raghav on ABBV-400 Plus 5-FU, Folinic Acid, and Bevacizumab in Previously Treated mCRC

“The study population is an unselected second-line population. All of these patients would have received at least 1 line of prior treatment with progression of disease. These patients are going to be irinotecan naive because irinotecan is a topoisomerase I inhibitor, and we are trying to see if ABBV-400’s activity is [higher].”

Kanwal PS Raghav, MBBS, MD, professor, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, discusses the study design of a phase 2 randomized trial (NCT06107413) evaluating ABBV-400, a c-MET–directed antibody-drug conjugate, in combination with fluorouracil (5-FU), folinic acid, and bevacizumab (Avastin) in patients with previously treated metastatic colorectal cancer (mCRC).

In this ongoing multicenter study, Raghav notes that investigators are assessing the safety, efficacy, and optimal dosing of ABBV-400 in an irinotecan-naïve, second-line mCRC population. The trial consists of two stages: an initial dose-escalation phase evaluating dosing regimens once every 2 weeks and once every 4 weeks, followed by a randomized dose-optimization phase comparing 2 ABBV-400 dosing schedules with standard-of-care FOLFIRI plus bevacizumab. Patients enrolled in the study have confirmed unresectable mCRC with measurable disease per RECIST 1.1 criteria and had previously progressed on first-line systemic therapy.

At the 2025 Gastrointestinal Cancers Symposium,Raghav presented the rationale for dose selection based on prior third-line studies utilizing an every-three-week ABBV-400 dosing schedule. In the initial safety lead-in cohort (n = 30), patients received ABBV-400 in combination with chemotherapy at varying dose levels to establish tolerability. The randomized expansion phase is evaluating the 2 optimal dosing schedules in comparison with standard treatment. Tumor assessments are conducted every 5 weeks for the first 6 months and every 8 weeks thereafter.

The trial’s primary efficacy end points are objective response rate (ORR) and progression-free survival (PFS) per RECIST 1.1 crtieria. Secondary end points include duration of response (DOR), disease control rate (DCR), overall survival (OS), and safety outcomes. Pharmacokinetic analyses and exploratory biomarker studies are also being conducted to assess ABBV-400 activity in this patient population.