Multinational phase 1 trial of telisotuzumab adizutecan for late-line colorectal cancer and advanced solid tumors

The antibody-drug conjugate telisotuzumab adizutecan (Temab-A) comprises the c-Met-targeting antibody telisotuzumab conjugated to the topoisomerase 1 iinhibitor payload, adizutecan. A multinational first-in-human phase 1 trial evaluates Temab-A in patients with progressive advanced solid tumors. Results from all patients in dose escalation and the metastatic colorectal cancer (mCRC) dose expansion have now been published. In total, 57 patients received at least one dose of Temab-A in dose escalation; 3.0 mg/kg once every 3 weeks was established as the maximum tolerated dose. Collectively, in dose escalation and dose expansion, 122 mCRC patients received Temab-A. All patients experienced at least one treatment-emergent adverse event; the most frequent were gastrointestinal (78%) and hematologic (71%) toxicities. TEAE-related discontinuations (10%) and deaths (3%) were infrequent. Across all doses in mCRC patients, overall response rate was 15.6% (95% CI 9.6-23.2), disease control rate was 74.6% (65.9-82.0), duration of response was 5.9 months (4.1-10.5), median progression-free survival was 4.6 months (4.0-5.4), and median overall survival was 10.4 months (8.9-13.1). The authors conclude that Temab-A has a tolerable and manageable safety profile, with promising antitumor activity.