FDA Grants Breakthrough Therapy Designations to AbbVie's Temab-A in Colorectal and Lung Cancers

The FDA has granted two Breakthrough Therapy Designations to telisotuzumab adizutecan (Temab-A, also known as ABBV-400), an investigational antibody-drug conjugate (ADC) from AbbVie, for use in metastatic colorectal cancer and non-small cell lung cancer (NSCLC), according to a press release from the company.

The designations, announced Oct. 7, mark the first time Temab-A has received breakthrough status from the agency, bringing AbbVie's broader ADC portfolio to four total Breakthrough Therapy Designations. One designation applies to Temab-A in combination with the targeted therapy bevacizumab (Avastin) for adults with refractory, metastatic colorectal cancer who have already been treated with fluoropyrimidine-, irinotecan- and oxaliplatin-based chemotherapy, an anti-VEGF antibody and, when appropriate, an anti-EGFR antibody. The second applies to Temab-A used alone in adults with locally advanced or metastatic, EGFR wild-type, non-squamous non-small cell lung cancer (NSCLC) whose tumors express the c-Met protein and who have previously received platinum-based chemotherapy and an anti-PD-(L)1 antibody.

What Is Temab-A?

Temab-A is a humanized antibody-drug conjugate that targets c-Met, a protein found on the surface of some cancer cells, and delivers a topoisomerase 1 inhibitor payload directly to those cells through a cleavable linker. The goal of this ADC design is to kill cancer cells while limiting damage to healthy tissue, compared with traditional chemotherapy.

The designations are based largely on data from M21-404 (NCT05029882), the first-in-human phase 1 study of Temab-A. In results published in the Journal of Clinical Oncology earlier this year, 122 patients with BRAF wild-type, microsatellite-stable metastatic colorectal cancer who received Temab-A across the dose-escalation and dose-expansion portions of the trial had an objective response rate of 15.6% and a disease control rate of 74.6%. Median progression-free survival was 4.6 months, median overall survival was 10.4 months, and responses lasted a median of 5.9 months. The most common side effects were gastrointestinal and blood-related (hematologic) in nature; 10% of patients stopped treatment because of side effects, and 3% died from treatment-related causes.

In lung cancer, AbbVie is studying Temab-A both as a monotherapy and in combination with a PD-1 inhibitor through the phase 1b/2 M24-536 trial, which is evaluating the drug as a potential chemotherapy-free, first-line option for patients with advanced non-squamous NSCLC who do not have an actionable genetic mutation driving their disease. That study is also examining c-Met and PD-L1 expression levels to help identify which patients are most likely to benefit. Temab-A is being tested separately in EGFR-mutated NSCLC as well, including in combination with osimertinib (Tagrisso).

What a Breakthrough Therapy Designation Means for Patients

A Breakthrough Therapy Designation is one of several tools the FDA uses to speed the development and review of drugs that show early evidence of a substantial improvement over available therapies on a clinically meaningful outcome. It does not mean a drug has been approved or that it is yet available outside of a clinical trial; instead, it allows the drug's developer closer, more frequent guidance from the FDA, with the goal of getting a promising treatment through the testing and review process more efficiently. Temab-A remains investigational and has not been approved by the FDA or any other regulatory agency.

“[Temab-A] has demonstrated potential across multiple tumor types, both as a monotherapy and in combinations,” Eleni Lagkadinou, M.D., Ph.D., vice president of oncology early development at AbbVie, said in the press release. She added that the new designations reflect growing clinical evidence supporting c-Met as a therapeutic target across solid tumors.

Beyond colorectal and lung cancers, AbbVie is evaluating Temab-A across several other hard-to-treat solid tumors, including head and neck squamous cell carcinoma, gastroesophageal adenocarcinoma, pancreatic ductal adenocarcinoma and ovarian cancer, in a series of phase 3 and phase 2/3 trials, both as a single agent and in combination with other therapies.

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