Dr Raghav on the Mechanism of Action of Telisotuzumab Adizutecan in ctDNA+ CRC

“[Temab-A] is a MET antibody-drug conjugate. MET is a protein which is found ubiquitously on all CRC cells. Using that protein as a homing beacon, you can deliver a cytotoxic chemotherapy payload within the cells. This drug has already shown promising activity in stage IV disease and is currently being evaluated in larger, more definitive clinical trials.”

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 mechanism of action of telisotuzumab adizutecan (ABBV-400; Temab-A) monotherapy in patients with post-adjuvant circulating tumor DNA (ctDNA)–positive colorectal cancer (CRC).

Since established therapies that can improve outcomes in this setting have yet to be defined, the standard of care for patients with ctDNA-positive CRC is active surveillance, Raghav began.

Temab-A is a MET-directed antibody drug conjugate (ADC), Raghav explained. MET is found ubiquitously on all CRC cells and can be used as a target to deliver a cytotoxic chemotherapy payload within cancer cells, he said. Telisotuzumab adizutecan has shown activity in patients with stage IV CRC and is being examined in larger clinical trials, he added.

Findings from the first-in-human phase 1 study (NCT05029882) of Temab-A in patients with advanced solid tumors, including CRC, demonstrated that treatment with the agent led to an overall response rate of 16% in patients with CRC treated in the third line and beyond (n = 122). The clinical benefit rate (CBR) and 24-week CBR were 50% and 29%, respectively. The median duration of response was 5.5 months (95% CI, 4.1-not evaluable).

Moving telisotuzumab adizutecan into the ctDNA-positive setting could allow for cure to be achieved in the post-adjuvant setting when disease volume is low, Raghav concluded.

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.