On October 7, 2026, local time, AbbVie announced that the U.S. FDA has granted telisotuzumab adizutecan (Temab-A; ABBV-400) two breakthrough therapy designations (BTDs), for colorectal cancer (CRC) and non-small cell lung cancer (NSCLC), respectively.
Designation Highlights
Temab-A is an investigational next-generation, c-Met-targeting antibody-drug conjugate (ADC) carrying a novel topoisomerase 1 inhibitor (Top1i) payload, and is currently being studied in advanced solid tumors, including CRC and NSCLC.
This is the first BTD for Temab-A and further highlights the strength of AbbVie's ADC portfolio; the portfolio currently includes four BTDs in total.
Specific Indications for the Two BTDs
The two BTDs granted to Temab-A are:
One is in combination with bevacizumab for the treatment of adult patients with refractory metastatic CRC who have previously received fluoropyrimidine, irinotecan, oxaliplatin, an anti-VEGF monoclonal antibody (mAb), and, if indicated, anti-EGFR mAb therapy.
The other is for Temab-A monotherapy in adult patients with locally advanced or metastatic EGFR wild-type, c-Met protein-expressing non-squamous NSCLC who have previously received platinum-based chemotherapy and anti-PD-(L)1 antibody therapy.
These designations are primarily based on results from the first-in-human study M21-404 (NCT05029882).
Management Commentary
Eleni Lagkadinou, MD, PhD, Vice President, Early Oncology Development, AbbVie, said: "These breakthrough therapy designations reflect the growing clinical evidence supporting c-Met as an important therapeutic target across multiple solid tumors. As one of the most advanced assets in our next-generation ADC portfolio, Temab-A has shown potential across multiple tumor types, both as monotherapy and in combination. We believe these designations further support our strategy of advancing biomarker-driven therapies and underscore our commitment to developing transformative medicines for patients with difficult-to-treat cancers."
Disease Background and FDA BTD Program
Colorectal cancer and lung cancer together affect more than 4 million people globally each year and remain among the leading causes of cancer-related death. Despite advances in treatment, many patients with CRC and advanced NSCLC still experience disease progression, highlighting the urgent need for new treatment approaches.
The FDA's BTD program is designed to accelerate the development and review of investigational drugs with clinical evidence suggesting they may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints.
Temab-A remains an investigational asset and has not been approved for use by any global regulatory authority.
About Temab-A
Telisotuzumab adizutecan (Temab-A) is a next-generation, c-Met protein-targeting antibody-drug conjugate (ADC) carrying a topoisomerase 1 inhibitor (Top1i) payload, and is currently being studied in advanced solid tumors, including CRC and NSCLC. c-Met protein (also known as MET protein) is expressed at increased levels in many solid tumors and may promote disease progression and treatment resistance, further reinforcing its potential as a promising therapeutic target.
Temab-A is developed using AbbVie's adizutecan platform and combines a validated humanized bivalent IgG1 monoclonal antibody that binds with high affinity to c-Met protein with a Top1i payload via a cleavable valine-alanine linker and a stable bromoacetamide linkage. This design is intended to support targeted delivery while minimizing systemic payload release.
In addition to CRC and NSCLC, Temab-A is also being evaluated in multiple other advanced solid tumors, including head and neck squamous cell carcinoma (HNSCC), gastroesophageal adenocarcinoma (GEA), pancreatic ductal adenocarcinoma (PDAC), and ovarian cancer (OC). Its clinical development program includes multiple Phase 3 and Phase 2/3 studies evaluating Temab-A as monotherapy and in combination with other therapies in different treatment settings.
