AbbVie’s telisotuzumab adizutecan (Temab-A) receives two FDA Breakthrough Therapy Designations for colorectal cancer and NSCLC.
Written By: Creola Gonsalves, MS Biotech
Reviewed By: Pharmacally Editorial Team
AbbVie announced that the U.S. Food and Drug Administration has granted two Breakthrough Therapy Designations (BTDs) to telisotuzumab adizutecan (Temab-A; ABBV-400), an investigational, next-generation c-Met-directed antibody-drug conjugate (ADC), for colorectal cancer (CRC) and non-small cell lung cancer (NSCLC).
The designations represent the first BTDs for Temab-A and are primarily supported by findings from the first-in-human M21-404 study (NCT05029882).
Two Breakthrough Therapy Designations for Temab-A
The first designation covers Temab-A in combination with bevacizumab for adults with refractory metastatic CRC who have previously received fluoropyrimidine-, irinotecan-, and oxaliplatin-based chemotherapy, an anti-vascular endothelial growth factor (VEGF) monoclonal antibody, and, if indicated, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody.
The second designation covers Temab-A as monotherapy for adults with locally advanced or metastatic, EGFR wild-type, c-Met protein-expressing, non-squamous NSCLC who have previously received platinum-based chemotherapy and an anti-programmed cell death protein 1/programmed death ligand 1 (PD-(L)1) antibody therapy.
Both designations were primarily based on results from the M21-404 study, a first-in-human clinical study evaluating Temab-A in patients with advanced solid tumors.
Temab-A Is a c-Met-Directed Antibody-Drug Conjugate
Telisotuzumab adizutecan is an investigational ADC designed to target the c-Met protein, also known as MET, and deliver a topoisomerase 1 inhibitor (Top1i) payload to cancer cells.
Developed using AbbVie’s adizutecan platform, Temab-A combines a humanized bivalent IgG1 monoclonal antibody that binds with high affinity to c-Met with the Top1i payload through a cleavable valine-alanine linker and stable bromoacetamide attachment. According to AbbVie, this design is intended to support targeted payload delivery while minimizing systemic payload release.
The c-Met protein is expressed at increased levels in several solid tumors and may contribute to tumor progression and treatment resistance, providing a rationale for evaluating c-Met-directed therapies across multiple cancer types.
Clinical Development Across Multiple Solid Tumors
Temab-A is being investigated in advanced solid tumors beyond CRC and NSCLC. AbbVie is evaluating the ADC in head and neck squamous cell carcinoma (HNSCC), gastroesophageal adenocarcinoma (GEA), pancreatic ductal adenocarcinoma (PDAC), and ovarian cancer (OC).
The clinical development program includes multiple Phase 3 and Phase 2/3 studies evaluating Temab-A as both a monotherapy and in combination with other therapies across different treatment settings.
In NSCLC, the development program also includes studies evaluating Temab-A in combination approaches and in additional molecularly defined patient populations. AbbVie previously reported ongoing development of Temab-A in combination with a PD-1 inhibitor in advanced non-squamous NSCLC and in EGFR-mutated NSCLC.
FDA Breakthrough Therapy Designation
The FDA’s Breakthrough Therapy Designation is intended to expedite the development and review of investigational medicines when preliminary clinical evidence indicates that the therapy may demonstrate substantial improvement over available therapies on one or more clinically significant endpoints. The designation does not constitute FDA approval or establish that a drug is safe or effective for the designated use.
For Temab-A, the two designations provide regulatory recognition of the clinical evidence supporting its development in the specified CRC and NSCLC populations.
Temab-A Remains Investigational
Despite receiving two Breakthrough Therapy Designations, Temab-A remains an investigational medicine and has not been approved for use by global regulatory authorities. Further clinical development and regulatory review will be required to determine its safety, efficacy, and potential role in the treatment of patients with cancer.
The two FDA designations expand the regulatory development pathway for Temab-A in refractory metastatic CRC and previously treated EGFR wild-type, c-Met protein-expressing non-squamous NSCLC, while ongoing clinical studies continue to evaluate the ADC across a broader range of solid tumors.
Reference
AbbVie’s Telisotuzumab Adizutecan (Temab-A) Receives Two Breakthrough Therapy Designations from the U.S. FDA for CRC and NSCLC, AbbVie, 07 October 2026
Study to Assess Adverse Events and Change in Disease Activity in Adult Participants With Advanced Solid Tumors Receiving Intravenous (IV) ABBV-400 as Monotherapy and in Combination with IV Bevacizumab, ClinicalTrials.gov ID NCT05029882
About the Writer
Creola Gonsalves (Linkedin) is an M.S. Biotechnology postgraduate with a strong interest in clinical research, evidence interpretation, and healthcare writing, with a focus on translating life-science knowledge into meaningful real-world insights.
She is trained in Good Clinical Practice (GCP), clinical research principles, and critical interpretation of randomized clinical trials, with certifications from NIH and Stanford University.
Her research background in biotechnological applications and microbial research strengthens her ability to understand scientific evidence and develop clear, accurate, and research-driven healthcare content.