Telisotuzumab Vedotin-tllv Given Accelerated Approval for NSCLC

Prior data reported reported an ORR of 34.6% and a median DOR of 9.0 months for the indicated patient population.

The FDA has granted accelerated approval to telisotuzumab vedotin-tllv (Teliso-V; Emrelis) for use in adult patients with locally advanced and metastatic non-squamous, non-small cell lung cancer who have received prior systemic therapy and have high c-Met protein overexpression, according to a news release from AbbVie, the drug’s developer.¹

The approval is based on data from the phase 2 LUMINOSITY study (NCT03539536). Patients on the trial with high c-Met expression in NSCLC (n = 84) saw a 35% overall response rate (ORR; 95% CI, 24%-46%). The median duration of response (DOR) was 7.2 months (95% CI, 4.2-12).

The most common adverse events (AEs), present in at least 20% of patients, were peripheral neuropathy, fatigue, decreased appetite, and peripheral edema. The most frequent laboratory abnormalities of grade 3 or 4, reported in at least 2% of patients, were lymphocytopenia, hyperglycemia, increased alanine aminotransferase, increased gamma glutamyl transferase, hypophosphatemia, hyponatremia, decreased hemoglobin, and hypocalcemia.

“Despite the progress we have seen in the treatment of lung cancer, we need more options for people whose treatments stop working,” Upal Basu Roy, PhD, MPH, executive director of research of the LUNGevity Foundation, said in the release. “This approval is a welcomed targeted therapy for those with high c-Met protein overexpressing late-stage, non-small cell lung cancer who have seen very limited treatment innovation in the last decade.”

A Closer Look at Safety Data from LUMINOSITY

Prior data reported from LUMINOSITY reported an ORR of 34.6% (95% CI, 24.2%-46.2%) and a median DOR of 9.0 months (95% CI, 4.2-13.0) in patients with non-squamous EGFR-wildtype NSCLC with high c-Met overexpression.²

Median overall survival (OS) and progression free survival (PFS) were 14.6 months (95% CI, 9.2-25.6) and 5.5 months (95% CI, 4.1-8.3), respectively, for those patients.

The study, published in the Journal of Clinical Oncology, reported that the most common treatment-related adverse events (TRAEs) of any grade were peripheral neuropathy (30%), peripheral edema (16%), and fatigue (16%). The most common AEs of grade 3 or higher was peripheral neuropathy (7%). At the primary analysis, the median time to onset of response was 1.41 months (range, 1.0-7.4).

In total, 68 patients with high c-Met overexpression experienced TRAEs (81.0%), and 25 experienced grade 3 or higher TRAEs (29.8%). Grade 5 AEs that may be related to treatment were reported in 2 patients (1.2%).

TRAEs led to treatment discontinuation in 21.5% of patients with non-squamous EGFR-wildtype NSCLC. The TRAEs that most often led to discontinuation were pneumonitis (7.6%), peripheral sensory neuropathy (7.0%), peripheral sensorimotor neuropathy (2.3%), and interstitial lung disease (ILD; 1.2%). The median time to onset of ILD and peripheral neuropathy resulting in treatment discontinuation were 48 days (range, 7-344) and 222.5 days (range, 57-519), respectively. One death was considered related to ILD, and 2 were considered related to disease progression.

“[Telisotuzumab vedotin-tllv], AbbVie’s first internally developed solid tumor medicine and our first solid tumor FDA approval in lung cancer, is a testament to our commitment to develop cancer therapies that aim to improve the course of treatment for patients facing this challenging disease,” stated Roopal Thakkar, MD, executive vice president of research and development and chief scientific officer at AbbVie in the announcement. “Leveraging advanced technology and data science, we are growing our ADC portfolio designed to deliver the right medicines to the right patients in need across a range of difficult-to-treat tumors.”

References

1. U.S. FDA approves EMRELIS™ (telisotuzumab vedotin-tllv) for adults with previously treated advanced non-small cell lung cancer (NSCLC) with high c-Met protein overexpression. News release. AbbVie. May 14, 2025. Accessed May 14, 2025. https://news.abbvie.com/2025-05-14-U-S-FDA-Approves-EMRELIS-TM-telisotuzumab-vedotin-tllv-for-Adults-With-Previously-Treated-Advanced-Non-Small-Cell-Lung-Cancer-NSCLC-With-High-c-Met-Protein-Overexpression
2. Camidge DR, Bar J, Horinouchi H, et al. Telisotuzumab vedotin monotherapy in patients with previously treated c-Met protein-overexpressing advanced nonsquamous EGFR-wildtype non-small cell lung cancer in the phase II LUMINOSITY trial. J Clin Oncol. 2024;42(25):3000-3011. doi:10.1200/JCO.24.00720