The US Food and Drug Administration (FDA) has granted 2 Breakthrough Therapy Designations to telisotuzumab adizutecan (Temab-A; ABBV-400), an investigational c-Met–directed antibody-drug conjugate, covering previously treated adults with metastatic colorectal cancer (CRC) and a biomarker-defined population with advanced non–small cell lung cancer (NSCLC), announced in an AbbVie press release.
One designation covers Temab-A plus bevacizumab for adults with refractory metastatic CRC previously treated with fluoropyrimidine, irinotecan, oxaliplatin, an anti-VEGF monoclonal antibody, and, when indicated, anti-EGFR therapy. The second covers Temab-A monotherapy for adults with locally advanced or metastatic EGFR wild-type, c-Met protein–expressing, nonsquamous NSCLC previously treated with platinum-based chemotherapy and an anti–PD-(L)1 antibody.
The designations were based primarily on findings from the ongoing first-in-human phase 1 M21-404 trial (NCT05029882).
In a CRC dose-expansion analysis, 83 patients received Temab-A plus bevacizumab or standard-of-care trifluridine/tipiracil plus bevacizumab. Patients were not selected by c-Met expression. Among 30 patients receiving Temab-A 2.4 mg/kg plus bevacizumab, the confirmed objective response rate was 27%, compared with 0% among 20 evaluable patients receiving trifluridine/tipiracil plus bevacizumab. The 2.0-mg/kg Temab-A combination produced an objective response rate of 15%. Investigators identified the 2.4-mg/kg dose as having the most favorable benefit-risk profile.
Grade 3 or higher treatment-emergent adverse events occurred in 67% of patients receiving Temab-A 2.4 mg/kg plus bevacizumab and 65% receiving standard-of-care therapy. Common adverse events with the Temab-A regimen included anemia (63%), nausea (60%), neutropenia (53%), fatigue (43%), and vomiting (40%). Treatment-related adverse events led to discontinuation in 3% and 10% of patients, respectively.
Separate M21-404 dose-expansion data included 48 patients with EGFR wild-type, nonsquamous NSCLC whose disease had progressed after platinum chemotherapy, immune checkpoint inhibition, and/or targeted therapy. Patients received Temab-A 2.4 mg/kg or 3.0 mg/kg every 3 weeks, and c-Met protein expression was assessed centrally by immunohistochemistry. Grade 3 or higher treatment-emergent adverse events occurred in 63% of patients; hematologic and gastrointestinal events were the most common overall.
Breakthrough Therapy Designation is intended to expedite development and review when preliminary clinical evidence indicates a therapy may provide substantial improvement over available treatment on a clinically significant end point. It does not constitute FDA approval. Temab-A remains investigational and is not approved by regulatory authorities.
Sources
AbbVie. AbbVie’s Telisotuzumab Adizutecan (Temab-A) Receives Two Breakthrough Therapy Designations From the U.S. FDA for CRC and NSCLC.Published October 7, 2026.
Cecchini M, Cruz-Correa M, Han SW, et al. Telisotuzumab adizutecan (ABBV-400; Temab-A) in combination with bevacizumab vs standard of care in patients with 3L+ colorectal cancer: dose expansion results of a phase I study. Ann Oncol. 2025;36(suppl 2):S479-S480. doi:10.1016/j.annonc.2025.08.1306. Annals of Oncology
De Miguel M, Yamamoto N, Raimbourg J, et al. 1257MO ABBV-400, a c-Met protein-targeting antibody-drug conjugate (ADC), in patients (pts) with advanced EGFR wildtype (WT) non-squamous (NSQ) non-small cell lung cancer (NSCLC): results from a phase I study. Ann Oncol. 2024;35(suppl 2):S805-S806. doi:10.1016/j.annonc.2024.08.1314. Annals of Oncology
