Clinical Report: FDA Grants Temab-A Dual Breakthrough Status

Overview

The FDA granted two Breakthrough Therapy Designations to investigational telisotuzumab adizutecan (Temab-A; ABBV-400): in combination with bevacizumab for previously treated metastatic colorectal cancer (CRC), and as monotherapy for a biomarker-defined population with advanced non–small cell lung cancer (NSCLC). The designations were based primarily on the ongoing phase 1 M21-404 trial; Temab-A is not FDA-approved.

Background

Temab-A is an investigational c-Met–directed antibody-drug conjugate studied in advanced CRC and NSCLC. The CRC designation concerns patients whose disease has progressed after specified chemotherapy and anti-VEGF treatment, with anti-EGFR therapy when indicated. The NSCLC designation concerns patients with EGFR wild-type, c-Met protein–expressing, nonsquamous disease previously treated with platinum-based chemotherapy and anti–PD-(L)1 therapy. Breakthrough Therapy Designation is intended to expedite development and review when preliminary clinical evidence indicates potential substantial improvement over available treatment on a clinically significant endpoint; it is not FDA approval.

Data Highlights

Key Findings

• The FDA granted two Breakthrough Therapy Designations for Temab-A, one for combination treatment in refractory metastatic CRC and one for monotherapy in a defined advanced NSCLC population.
• The designations were based primarily on the ongoing first-in-human phase 1 M21-404 trial (NCT05029882).
• In the CRC dose-expansion analysis, patients were not selected by c-Met expression; the confirmed ORR was 27% with Temab-A 2.4 mg/kg plus bevacizumab versus 0% among evaluable patients receiving trifluridine/tipiracil plus bevacizumab.
• Grade 3 or higher TEAEs occurred in 67% of patients receiving the 2.4-mg/kg Temab-A combination and 65% receiving standard-of-care therapy; treatment-related adverse events led to discontinuation in 3% and 10%, respectively.
• In the NSCLC dose expansion, 48 patients with EGFR wild-type nonsquamous disease received Temab-A at 2.4 or 3.0 mg/kg every 3 weeks; grade 3 or higher TEAEs occurred in 63%.
• Breakthrough Therapy Designation does not constitute approval, and Temab-A remains investigational and unapproved by regulatory authorities.

Clinical Implications

The designations apply to the specific treatment settings and eligibility criteria described; they do not establish Temab-A as an approved treatment. The reported phase 1 dose-expansion findings provide the clinical evidence cited for the designations, while the source material does not report confirmatory efficacy results.

Conclusion

Temab-A received two FDA Breakthrough Therapy Designations based primarily on phase 1 evidence in previously treated CRC and biomarker-defined NSCLC. The agent remains investigational, and the designations are distinct from FDA approval.

Related Resources & Content

1. AbbVie, Company press release, 2026 — AbbVie’s Telisotuzumab Adizutecan (Temab-A) Receives Two Breakthrough Therapy Designations From the U.S. FDA for CRC and NSCLC
2. Cecchini M, Cruz-Correa M, Han SW, et al., Annals of Oncology, 2025 — 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
3. De Miguel M, Yamamoto N, Raimbourg J, et al., Annals of Oncology, 2024 — ABBV-400, a c-Met protein-targeting antibody-drug conjugate (ADC), in patients with advanced EGFR wildtype non-squamous NSCLC: results from a phase I study
4. The ASCO Post — FDA Approves Teclistamab and Daratumumab For Relapsed or Refractory Multiple Myeloma
5. the asco post — FDA Grants Accelerated Approval to Talquetamab-tgvs for Treatment of Relapsed or Refractory Multiple Myeloma
6. The ASCO Post — FDA Grants Breakthrough Therapy Designation to MPDL3280A for Non–Small Cell Lung Cancer
7. The ASCO Post — FDA Grants Accelerated Approval to Atezolizumab/Nab-Paclitaxel; Regular Approval Contingent on Confirmatory Trials
8. AbbVie’s Telisotuzumab Adizutecan (Temab-A) Receives Two Breakthrough Therapy Designations From the U.S. FDA for CRC and NSCLC
9. Therapy for Stage IV Non–Small Cell Lung Cancer With Driver Alterations: ASCO Living Guideline, Version 2026.3.2 | Journal of Clinical Oncology
10. Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up☆ - Annals of Oncology