Dr Raghav on a Phase 2 Study of ABBV-400 Plus Fluorouracil, Folinic Acid, and Bevacizumab in Pretreated Metastatic CRC

“The rationale of this second-line study is to combine ABBV-400 with 5-FU, folinic acid, and bevacizumab, which are the standard chemotherapy partners for second-line chemotherapy.”

Kanwal P.S. Raghav, MD, MBBS, clinical medical director, Division of Ambulatory Treatment Centers (MDACC), and associate professor, Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses a phase 2 study (NCT06107413) evaluating the safety and efficacy of ABBV-400 plus fluorouracil (5-FU), folinic acid, and bevacizumab (Avastin) in pretreated patients with metastatic colorectal cancer (mCRC).

ABBV-400 is a c-MET–directed antibody-drug conjugate composed of the monoclonal antibody telisotuzumab conjugated to a potent topoisomerase 1 inhibitor payload via a stable and cleavable linker, Raghav explains. The agent has previously been examined in the third-line setting in patients with treatment-refractory CRC, he adds. It displayed promising response rates in this study, supporting the evaluation of the drug in earlier settings where patients could potentially derive an even greater benefit. Raghav says that in earlier lines of treatment, patients will not have as much bone marrow suppression as they might in later lines.

To this end, a current phase 2 study is looking at ABBV-400 in combination with 5-FU, folinic acid, and bevacizumab as a treatment approach for patients with mCRC. Specifically, the multicenter, open-label, international study is enrolling adult patients with confirmed unresectable mCRC with measurable disease per RECIST 1.1 criteria whose disease is BRAF V600 wild-type and microsatellite stable or mismatch repair proficient. Patients are required to have an ECOG performance status of 0 or 1 and must have experienced disease progression on only 1 first-line systemic combination of chemotherapy in the metastatic setting, with or without an anti-VEGF or anti-EGFR agent.

The dual primary efficacy end points are objective response rate and progression-free survival. Safety end points consist of adverse effect monitoring, physical examinations, vital sign measurements, electrocardiogram variables, and clinical laboratory testing. Enrollment was initiated in November 2023, and 19 patients had been enrolled as of April 23, 2024.