AbbVie announced on October 7, 2026, that the U.S. Food and Drug Administration has granted two Breakthrough Therapy Designations for telisotuzumab adizutecan (Temab-A; ABBV-400), an investigational c-Met-directed antibody-drug conjugate. The designations cover two separate indications: Temab-A in combination with bevacizumab for refractory, metastatic colorectal cancer, and Temab-A as a monotherapy for locally advanced or metastatic EGFR wild-type, c-Met protein-expressing, non-squamous non-small cell lung cancer.
Both designations were primarily based on results from the first-in-human study M21-404 (NCT05029882). Specific response rates, survival data, and safety findings from that study were not disclosed in AbbVie’s announcement.
Key finding
The FDA granted telisotuzumab adizutecan two Breakthrough Therapy Designations — one in metastatic CRC in combination with bevacizumab, and one as monotherapy in EGFR wild-type, c-Met protein-expressing non-squamous NSCLC — based on early clinical evidence from study M21-404, though numerical efficacy and safety data supporting these designations were not publicly disclosed.
Study Design
| Trial | M21-404 (NCT05029882); first-in-human study |
|---|---|
| Population | Adults with advanced solid tumors, including refractory metastatic CRC and locally advanced or metastatic EGFR wild-type, c-Met protein-expressing non-squamous NSCLC |
| Treatment | Telisotuzumab adizutecan as monotherapy and in combination with bevacizumab across tumor types |
M21-404 is the first-in-human trial evaluating Temab-A across multiple advanced solid tumors. AbbVie stated that findings from this study provided the primary clinical basis for both Breakthrough Therapy Designations. Primary and secondary endpoint specifications, as well as detailed study design parameters, were not disclosed in the announcement.
Results and Safety
AbbVie’s announcement did not include specific efficacy or safety data from M21-404. Numerical response rates, progression-free survival, overall survival, or adverse event profiles were also not reported. The company indicated only that the clinical evidence from the study was sufficient for the FDA to determine that Temab-A may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints — the standard threshold for Breakthrough Therapy Designation.
AbbVie noted that Temab-A has shown potential across multiple tumor types both as a monotherapy and in combination regimens, but quantitative data supporting that characterization were not made available in this release.
Clinical Context
Colorectal and lung cancers together affect more than four million people worldwide annually and remain among the leading causes of cancer-related mortality. In both CRC and advanced NSCLC, many patients continue to experience disease progression despite available therapies, creating an ongoing need for new treatment approaches. The c-Met protein, which is overexpressed in numerous solid tumors, has been identified as a potential driver of disease progression and treatment resistance, making it an attractive ADC target.
These two designations represent the first BTDs granted for Temab-A and bring AbbVie’s total ADC-related BTDs to four. Beyond CRC and NSCLC, Temab-A is under investigation in head and neck squamous cell carcinoma, gastroesophageal adenocarcinoma, pancreatic ductal adenocarcinoma, and ovarian cancer, with multiple Phase 2/3 and Phase 3 studies ongoing. Temab-A has not been approved by any global regulatory authority, and its clinical benefit remains to be established in randomized controlled trials.
Sources
- AbbVie. “AbbVie’s Telisotuzumab Adizutecan (Temab-A) Receives Two Breakthrough Therapy Designations From the U.S. FDA for CRC and NSCLC.” Press release. October 7, 2026. View source.
AI disclosure: This article was prepared with assistance from generative AI using the source material cited above. It was reviewed and edited by Hailey Pash, MSN, APN before publication.
