c-Met ADC Temab-A Gains 2 FDA Breakthrough Designations in CRC, NSCLC

Telisotuzumab adizutecan (Temab-A), an investigational c-Met–directed antibody-drug conjugate (ADC), has received 2 breakthrough therapy designations (BTDs) from the FDA for colorectal cancer (CRC) and non–small cell lung cancer (NSCLC).¹

The first designation applies to Temab-A in combination with bevacizumab (Avastin) for adults with refractory metastatic CRC who have previously received fluoropyrimidine, irinotecan, oxaliplatin, an anti-VEGF monoclonal antibody, and, when indicated, an anti-EGFR monoclonal antibody. The second designation covers Temab-A monotherapy for adults with locally advanced or metastatic EGFR wild-type, c-Met protein–expressing, nonsquamous NSCLC following treatment with platinum-based chemotherapy and an anti–PD-(L)1 antibody.

"These [BTDs] reflect the growing clinical evidence supporting c-Met as a meaningful therapeutic target across multiple solid tumors," Eleni Lagkadinou, MD, PhD, vice president, oncology early development at AbbVie, stated in a news release. "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. 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."

The FDA's BTD program is intended to expedite the development and review of investigational therapies for serious or life-threatening diseases when preliminary clinical evidence indicates the potential for substantial improvement over available therapies on clinically significant end points. For Temab-A, the 2 designations reflect development in heavily pretreated populations in which treatment options may be limited.

Temab-A: Mechanistic Rationale

Telisotuzumab adizutecan is a next-generation ADC designed to target c-Met protein, also known as MET protein. The target is expressed at increased levels in multiple solid tumors and may contribute to disease progression and treatment resistance.

The ADC combines a humanized, bivalent IgG1 monoclonal antibody that binds c-Met with a topoisomerase 1 inhibitor payload connected through a cleavable linker and a stable bromoacetamide attachment. This structure is intended to facilitate targeted delivery of the cytotoxic payload while limiting systemic payload release.

Clinical Development of Temab-A

Both designations were primarily supported by findings from the first-in-human phase 1 study M21-404 (NCT05029882). The open-label, multicenter study is evaluating the safety, tolerability, pharmacokinetics, and antitumor activity of intravenous Temab-A as monotherapy and in combination with bevacizumab in adults with advanced solid tumors.²

The study includes a dose-escalation phase followed by dose-expansion cohorts designed to further evaluate the recommended phase 2 dose and selected treatment combinations. Approximately 500 participants are planned for enrollment across the study, with patients receiving treatment and undergoing regular clinical assessments, laboratory testing, and monitoring for adverse events and changes in disease activity.

In addition to CRC and NSCLC, Temab-A’s development program includes head and neck squamous cell carcinoma, gastroesophageal adenocarcinoma, pancreatic ductal adenocarcinoma (PDAC), and ovarian cancer. Prior data presented at the 2025 European Society for Medical Oncology (ESMO) Congress have demonstrated activity with Temab-A in PDAC. In a phase 1 basket study, treatment produced a confirmed objective response rate of 23.8% and a confirmed clinical benefit rate of 81.0% among 42 patients with previously treated locally advanced or metastatic disease.³ Median progression-free survival was 5.4 months, and median overall survival was 7.9 months.

REFERENCES

1. AbbVie's Telisotuzumab Adizutecan (Temab-A) Receives Two Breakthrough Therapy Designations From the U.S. FDA for CRC and NSCLC. News release. AbbVie. October 7, 2026. Accessed October 8, 2026. https://tinyurl.com/aaaxyxt9

2. 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. Updated October 29, 2025. Accessed October 8, 2026. https://clinicaltrials.gov/study/NCT05029882

3. Harding JJ, Strickler J, Henry J, et al. Phase 1 basket study of telisotuzumab adizutecan (ABBV-400; Temab-A), a c-Met protein–targeting antibody-drug conjugate: results from patients with pancreatic ductal adenocarcinoma. Presented at the European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract 2214MO.