AbbVie announced October 7, 2026, that FDA has granted 2 breakthrough therapy designations for telisotuzumab adizutecan (Temab-A; ABBV-400), an investigational, c-Met-directed antibody-drug conjugate (ADC), in colorectal cancer (CRC) and non-small cell lung cancer (NSCLC).¹ The designations are the first breakthrough therapy designations for Temab-A and bring AbbVie's ADC portfolio to 4 products with this designation.¹
Key facts
- Drug: Temab-A (ABBV-400; AbbVie)
- Drug type: c-Met-directed ADC
- Payload: Top1i, attached via a cleavable valine-alanine linker
- Designations: 2 FDA breakthrough therapy designations (CRC + bevacizumab) and NSCLC (monotherapy)
- Supporting trial: First-in-human study M21-404 (NCT05029882)
- CRC efficacy: 15.6% ORR; 74.6% disease control rate; 4.6-month median PFS
- Recommended phase 2 dose: 2.4 mg/kg every 3 weeks
- Additional indications studied: Head and neck, gastroesophageal, pancreatic, and ovarian cancers
"These [b]reakthrough [t]herapy [d]esignations reflect the growing clinical evidence supporting c-Met as a meaningful therapeutic target across multiple solid tumors," said Eleni Lagkadinou, MD, PhD, vice president, oncology early development, AbbVie, in a company press release.¹ "As one of the most advanced assets in our next-generation ADC portfolio, Temab-A has demonstrated potential across multiple tumor types, both as a monotherapy and in combinations."
What is Temab-A, and how does it work?
Temab-A is a next-generation ADC that pairs a humanized, bivalent IgG1 monoclonal antibody targeting the c-Met protein with a topoisomerase 1 inhibitor (Top1i) payload, linked through a cleavable valine-alanine linker with stable bromoacetamide attachment. The c-Met protein, overexpressed in many solid tumors, has been implicated in disease progression and treatment resistance, reinforcing interest in it as a therapeutic target across tumor types.¹
What are the terms of the 2 designations?
The CRC designation covers Temab-A in combination with bevacizumab for adults with refractory, metastatic disease previously treated with fluoropyrimidine, irinotecan, oxaliplatin, an anti-vascular endothelial growth factor monoclonal antibody, and, if indicated, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody. The NSCLC designation covers Temab-A as monotherapy for adults with locally advanced or metastatic, EGFR wild-type, c-Met-expressing, non-squamous disease previously treated with platinum-based chemotherapy and an anti-programmed cell death protein/ligand 1 antibody. Both designations were based primarily on results from the first-in-human study M21-404 (NCT05029882).¹
What clinical data support the CRC designation?
A peer-reviewed report of the M21-404 trial's colorectal cancer cohort found an overall response rate (ORR) of 15.6% among heavily pretreated patients, rising to 24.4% at the 3.0-mg/kg dose, with a disease control rate of 74.6%, a median progression-free survival (PFS) of 4.6 months, and a median overall survival of 10.4 months.² Among patients who responded, the median duration of response was 5.9 months, and the study established 2.4 mg/kg every 3 weeks as the recommended phase 2 dose balancing tolerability against antitumor activity in this third-line-or-later setting.²
