Dr Raghav on the Rationale for Investigating Telisotuzumab Adizutecan in ctDNA+ CRC

“The question is whether you can use that MRD window to bring about curative therapies in this setting, and that's where most of our clinical trials are going. Our clinical trial is utilizing one such novel therapeutic which has already established efficacy in stage IV metastatic CRC, [Temab-A], a MET antibody-drug conjugate.”

Kanwal P.S. Raghav, MBBS, MD, a professor in the Department of Gastrointestinal (GI) Medical Oncology, Division of Cancer Medicine, as well as the associate vice president (AVP) and executive medical director (EMD) of the Department of Ambulatory Medical Operations at The University of Texas MD Anderson Cancer Center, discussed the rationale for evaluating telisotuzumab adizutecan (ABBV-400; Temab-A) as monotherapy in patients with post-adjuvant circulating tumor DNA (ctDNA)–positive colorectal cancer (CRC).

ctDNA has been established as a marker for disease relapse in CRC and other disease areas, Raghav began. Both observational and prospective data have shown that patients with ctDNA positivity are at a high risk of disease recurrence and recent data have shown that longitudinal testing can enhance testing sensitivity, he added. Accordingly, investigators are working to determine if the minimal residual disease window can be used to introduce curative therapies, he explained.

One of these trials is a phase 2 study (NCT07023289) of the MET-directed antibody-drug conjugate Temab-A, Raghav said. The global, open-label, randomized trial is enrolling adult patients with histologically or cytologically confirmed adenocarcinoma of the colon or rectum.

Patients will be randomly assigned 1:1 to receive intravenous telisotuzumab adizutecan at 2.4 mg/kg every 3 weeks or active surveillance for 9 months. ctDNA testing will be conducted on day 1 of cycles 2, 3, and 4, as well as at months 6 and 9.

The study’s primary end point is disease-free survival. Secondary end points include ctDNA clearance at 6 months and overall survival.

Disclosures: Raghav received honoraria from Bayer, Daiichi Sankyo/Astra Zeneca, Eisai, Merck, and Seagen. He also holds consulting or advisory roles with Bayer, Daiichi Sankyo/Astra Zeneca, Eisai, Merck, and Seagen. He received institutional research funding from Abbvie, Bayer, Daiichi Sankyo/Astra Zeneca, Eisai, Guardant Health, HiberCell, Innovent Biologics, Janssen, Merck Serono, Roche/Genentech, UCB, and Xencor.