Dr Raghav on Data Interpretation Standards in ctDNA+ CRC Clinical Trials

“Most patients are going to be asymptomatic; therefore, it is very important that the drugs that we bring into this space have promising efficacy. We need to have a higher threshold in this space. If you give [patients a therapy with] a lot of toxicities without affording them cures, then that would not be a palatable situation.”

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 standards for data interpretation in clinical trials involving circulating tumor DNA (ctDNA) testing in colorectal cancer.

Most patients with minimal residual disease (MRD) positivity are asymptomatic and will not have radiographic evidence of disease, Raghav began. Therefore, it is paramount that agents given in this space have promising efficacy with a higher threshold for activity, he said. Administering a therapy with added toxicity that does not ultimately lead to disease cure would not be palatable for patients in this setting, he noted.

In the MRD-positive setting, toxicity is an important criterion for data interpretation, Raghav explained. However, patients with ctDNA-positive disease have a high chance of experiencing disease recurrence so the tradeoff of risking toxicity for the potential of cure is usually acceptable, he concluded.

Findings from the first-in-human phase 1 study (NCT05029882) of telisotuzumab adizutecan (ABBV-400) in patients with advanced solid tumors, including CRC, revealed that any-grade treatment-emergent adverse effects (TEAEs) occurred in all patients with CRC who received the agent (n = 122). Grade 3 or higher TEAEs were reported at a rate of 71%.

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.