Dr Strickler on the Rationale for Evaluating Temab-A in Chemo-Refractory Metastatic CRC

“One very promising therapy that’s entering the clinic and is still under investigation is an antibody-drug conjugate that targets c-Met but is linked to a topoisomerase 1 inhibitor. We’ve already seen preliminary signals of significant activity in patients with chemotherapy-refractory metastatic colorectal cancer, and it appears to be fairly well tolerated.”

John H. Strickler, MD, a professor of medicine in the Division of Medical Oncology, a coleader for the Precision Cancer Medicine and Investigational Therapeutics Program, and the associate director of Clinical Research — GI Oncology at the Duke Cancer Institute, detailed the rationale of a phase 3 trial (NCT05029882) evaluating the antibody-drug conjugate (ADC) telisotuzumab adizutecan (Temab-A; ABBV-400) for the treatment of patients with refractory metastatic colorectal cancer (CRC) with increased c-Met protein expression.

Overall survival data have shown improvement in patients with metastatic CRC; however, there is still a lot of work that needs to be done, especially for patients who are refractory to chemotherapy, Strickler began. Temab-A is currently being evaluated and has demonstrated preliminary signals of significant activity for the treatment of patients with chemotherapy-refractory metastatic CRC; the agent is also well tolerated, he explained. Of note, patients with higher levels of c-Met expression tend to respond better to Temab-A, he added. Therefore, the rationale of the study was to investigate Temab-A for the treatment of patients with c-MET–high disease, defined as an immunohistochemistry 3+ in more than 10% of cells, compared with patients treated with standard of care (SOC) trifluridine (Viroptic)/tipiracil plus bevacizumab (Avastin), he concluded.

The global, open-label, randomized study enrolled 62 patients as of April 2025. However, the study is anticipated to include approximately 60 patients in stage 1 of the trial, randomly assigning patients 1:1 to 2 separate doses of Temab-A. In stage 2 of the trial, approximately 400 patients will be enrolled, who will be randomly assigned 1:1 to the optimal dose of the Temab-A arm or the SOC arm.