A phase 2 clinical trial (NCT06107413) is currently underway to assess the efficacy and safety of ABBV-400, an antibody-drug conjugate targeting c-MET, in combination with fluorouracil (5-FU), folinic acid, and bevacizumab for patients with pretreated metastatic colorectal cancer (mCRC). This multicenter study seeks to determine the optimal dosing regimen of ABBV-400 and its potential to improve outcomes in patients who have progressed on prior first-line systemic therapy.
The trial design incorporates an initial dose-escalation phase, evaluating ABBV-400 dosing schedules administered once every two weeks and once every four weeks. Following the dose escalation, a randomized dose-optimization phase will compare two ABBV-400 dosing schedules against the standard-of-care FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus bevacizumab. Patients enrolled have confirmed unresectable mCRC with measurable disease per RECIST 1.1 criteria and must be irinotecan-naive, having progressed on a first-line systemic therapy.
Rationale and Endpoints
Dr. Kanwal P.S. Raghav, MD, MBBS, from The University of Texas MD Anderson Cancer Center, presented the rationale for dose selection based on prior third-line studies utilizing an every-three-week ABBV-400 dosing schedule at the 2025 Gastrointestinal Cancers Symposium. The initial safety lead-in cohort (n = 30) 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 primary efficacy endpoints of the trial are objective response rate (ORR) and progression-free survival (PFS) as assessed by RECIST 1.1 criteria. Secondary endpoints 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 further understand ABBV-400's activity in this patient population.
Significance
Metastatic colorectal cancer remains a significant clinical challenge, with many patients experiencing disease progression after first-line treatment. This study aims to provide insights into the potential benefits of ABBV-400 in combination with established chemotherapy regimens for patients who have limited treatment options. By focusing on an irinotecan-naive population, the trial seeks to determine if ABBV-400 can offer a new therapeutic avenue for these patients.
