FDA Grants Breakthrough Therapy Designation to Temab-A in Previously Treated c-Met–Expressing Nonsquamous NSCLC

The FDA has granted breakthrough therapy designation to telisotuzumab adizutecan (Temab-A; ABBV-400) monotherapy for the treatment of patients with previously treated, c-Met–expressing, EGFR wild-type nonsquamous non–small cell lung cancer (NSCLC) whose disease has progressed on platinum-based chemotherapy and anti–PD-(L)1 therapy.¹

The designation was primarily based on results from the first-in-human phase 1 study M21-404 (NCT05029882).^1,2 In the total population of patients with EGFR wild-type nonsquamous NSCLC (n = 48), the objective response rate (ORR) was 47.9%, and enrichment for ORR was seen in patients with higher c-Met protein expression, although responses were also observed in patients with biomarker-negative tumors.² Among patients in the total population with immunohistochemistry (IHC) results (n = 47), the ORR was 48.9%. Among patients with c-Met protein expression on at least 50% of cells (n = 37) and less than 50% of cells (n = 10) per IHC 2+, the ORRs were 51.4% and 40.0%, respectively. Among patients with c-Met protein expression on at least 25% of cells (n = 15) and less than 25% of cells (n = 32) per IHC 3+, the ORRs were 60.0% and 43.8%, respectively. Among patients with c-Met protein expression on at least 50% of cells (n = 9) and less than 50% of cells (n = 38) per IHC 3+, the ORRs were 77.8% and 42.1%, respectively.

“[This] breakthrough therapy [designation reflects] the growing clinical evidence supporting c-Met as a meaningful therapeutic target across multiple solid tumors,” Eleni Lagkadinou, MD, PhD, vice president of oncology early development at AbbVie, stated in a news release.¹

Temab-A is an investigational c-Met–directed antibody-drug conjugate with a topoisomerase 1 inhibitor payload.

How has Temab-A performed in patients with EGFR-mutated NSCLC?

Separately, in the EGFR-mutated nonsquamous NSCLC cohort of study M21-404, data presented at the 2025 ASCO Annual Meeting demonstrated that Temab-A produced a confirmed ORR of 63.4% (95% CI, 46.9%-77.9%) among 41 patients with third-line or later disease.³

Among the patients in the EGFR-mutated cohort, 78% had previously received osimertinib (Tagrisso), and 34% had brain metastases at baseline. Patients had received a median of 3 prior lines of therapy (range, 1-8).

The clinical benefit rate was 93%, including rates of 83% at 12 weeks and 78% at 24 weeks. The median duration of response was 9.8 months (95% CI, 8.3-13.9), the median progression-free survival was 10.9 months (95% CI, 9.4-12.3), and the estimated 12-month overall survival rate was 69% (95% CI, 52%-81%).

Responses occurred irrespective of EGFR alteration type and resistance mechanism. The ORR was 69.2% (95% CI, 38.6%-90.9%) in patients with EGFR T790M (n = 13) mutations and 57.1% (95% CI, 18.4%-90.1%) in those with EGFR C797X (n = 7) mutations or focal MET amplification (n = 7). The ORR was 56.3% (95% CI, 37.7%-73.6%) in patients who were previously treated with osimertinib (n = 32) vs 88.9% (95% CI, 51.8%-99.7%) in those who were not (n = 9), and 57.1% (95% CI, 28.9%-82.3%) in patients with baseline brain metastases (n = 14) vs 66.7% (95% CI, 46.0%-83.5%) in those without (n = 27).

Of 39 patients with available c-Met IHC results (n = 39), the ORR was 70% in those with at least 25% of cells with 2+ staining (n = 33) vs 33% in those below that threshold (n = 6); using a 3+ threshold, the ORRs were 68% (n = 19) vs 60% (n = 20), respectively.

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 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. de Miguel M, Yamamoto N, Raimbourg J, et al. Telisotuzumab adizutecan in patients with advanced EGFR wild-type nonsquamous NSCLC: results from a phase 1 study. Ann Oncol. 2024;35(suppl 2):S805-S806. doi:10.1016/j.annonc.2024.08.1314
3. Camidge DR, Raimbourg J, Lee YG, et al. Telisotuzumab adizutecan (ABBV-400; Temab-A), a c-Met protein–targeting antibody-drug conjugate (ADC), in patients (pts) with advanced EGFR-mutated (MT) non-squamous (NSQ) non-small cell lung cancer (NSCLC): Results from a phase 1 study. J Clin Oncol. 2025;43(suppl 16):8512. doi:10.1200/JCO.2025.43.16_suppl.8512