AbbVie's Temab-A Gets 2 FDA Breakthrough Tags for CRC, NSCLC

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

"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

What does this mean for AbbVie's broader ADC pipeline?

Beyond CRC and NSCLC, Temab-A is being evaluated in head and neck squamous cell carcinoma, gastroesophageal adenocarcinoma, pancreatic ductal adenocarcinoma, and ovarian cancer across multiple phase 3 and phase 2/3 studies as both monotherapy and in combination regimens. AbbVie said it is evaluating more than 35 investigational oncology medicines overall, spanning small-molecule therapeutics, ADCs, immuno-oncology agents, multispecific antibodies, and cell therapy platforms.¹ Colorectal and lung cancer together are diagnosed in more than 4 million people worldwide each year and remain among the leading causes of cancer-related mortality, underscoring demand for new therapeutic approaches despite existing treatment advances.¹^,³^,⁴

What are the limitations?

Temab-A remains investigational and has not been approved by any global regulatory authority. Breakthrough therapy status does not guarantee eventual approval. The cited CRC efficacy data come from a single-arm, dose-finding phase 1 study rather than a randomized trial, and no peer-reviewed efficacy data specific to the EGFR wild-type NSCLC population underlying the second designation have yet been published.

References

1. AbbVie. AbbVie's Telisotuzumab Adizutecan (Temab-A) receives two breakthrough therapy designations from the US FDA for CRC and NSCLC. Press release. Published October 7, 2026. Accessed October 7, 2026. https://news.abbvie.com/2026-10-07-AbbVies-Telisotuzumab-Adizutecan-Temab-A-Receives-Two-Breakthrough-Therapy-Designations-From-the-U-S-FDA-for-CRC-and-NSCLC
2. Sharma MR, Powderly J, Kuboki Y, et al. Phase I study of telisotuzumab adizutecan (Temab-A, ABBV-400), a novel c-Met antibody-drug conjugate, in patients with late-line colorectal cancer and advanced solid tumors. J Clin Oncol. 2026;44(20):1876-1888. doi:10.1200/JCO-25-01525
3. International Agency for Research on Cancer. Lung cancer awareness month 2024. Published November 4, 2024. Accessed October 7, 2026. https://www.iarc.who.int/featured-news/lung-cancer-awareness-month-2024/
4. World Health Organization. Colorectal cancer. Published February 13, 2026. Accessed October 7, 2026. https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer