Phase I Study of Telisotuzumab Adizutecan (Temab-A, ABBV-400), a Novel c-Met Antibody-Drug Conjugate, in Patients With Late-Line Colorectal Cancer and Advanced Solid Tumors.

PURPOSE: The antibody-drug conjugate Temab-A comprises the c-Met-targeting antibody telisotuzumab conjugated to a novel topoisomerase 1 inhibitor payload, adizutecan. A first-in-human phase I study (ClinicalTrials.gov identifier: NCT05029882) of Temab-A in patients with advanced solid tumors whose disease has progressed is currently ongoing. We report results from all patients in the dose escalation and the monotherapy metastatic colorectal cancer (mCRC) dose expansion. METHODS: wild-type, microsatellite stable/mismatch repair-proficient mCRC were randomly assigned to 1.6 mg/kg, 2.4 mg/kg, or 3.0 mg/kg Temab-A once every 3 weeks. Primary end points included safety, pharmacokinetics, recommended phase II dose of Temab-A monotherapy, and Temab-A efficacy in patients with mCRC. RESULTS: In total, 57 patients received ≥1 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 patients with mCRC received Temab-A (dose escalation, N = 29; randomized dose optimization expansion, N = 93). All patients experienced ≥1 treatment-emergent adverse event; the most frequent were gastrointestinal (78%) and hematologic (71%) toxicities. Treatment-related discontinuations and deaths were infrequent (10% and 3%, respectively). Across all doses in patients with mCRC, overall response rate was 15.6% (95% CI, 9.6 to 23.2), disease control rate was 74.6% (95% CI, 65.9 to 82.0), and duration of response was 5.9 months (95% CI, 4.1 to 10.5); responses were more frequent at doses of 2.4 mg/kg and 3.0 mg/kg once every 3 weeks. Median progression-free survival was 4.6 months (95% CI: 4.0, 5.4), and median overall survival was 10.4 months (95% CI, 8.9 to 13.1). CONCLUSION: Temab-A at 2.4 mg/kg once every 3 weeks has a tolerable and manageable safety profile, with promising antitumor activity.