Teliso-V Approved to Treat Advanced NSCLC With High c-Met Protein Overexpression

The FDA approved telisotuzumab vedotin-tllv (Emrelis; AbbVie) to treat adults with locally advanced or metastatic, non-squamous non–small cell lung cancer (NSCLC) with high c-Met protein overexpression who have received a prior systemic treatment.¹

Also referred to as Teliso-V, telisotuzumab vedotin is an antibody-drug conjugate (ADC) that targets surface c-MET expression, which affects roughly a quarter of patients with EGFR wild-type NSCLC.² Telisotuzumab vedotin is now the only approved treatment for this indication, according to an AbbVie news release, providing a new option for these patients based on efficacy and safety data from the ongoing phase 2 LUMINOSITY trial (NCT03539536).^1,3

The FDA approved telisotuzumab vedotin based on data from the ongoing LUMINOSITY trial. | Image credit: chrisdorney – stock.adobe.com

"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 at the LUNGevity Foundation, said in a news release.¹ "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."

High c-Met protein overexpression happens when at least 50% of tumor cells have strong staining (3+). The LUMINOSITY trial demonstrated a 35% overall response rate (95% CI, 24-46) and a duration of response of 7.2 months on average (95% CI, 4.2-12) among the 84 patients with high c-Met protein overexpression who took telisotuzumab vedotin.

The most common adverse events among the cohort were peripheral neuropathy, fatigue, decreased appetite, and peripheral edema. The most common Grade 3 or 4 laboratory abnormalities included decreased lymphocytes, increased glucose, increased alanine aminotransferase, increased gamma glutamyl transferase, decreased phosphorus, decreased sodium, decreased hemoglobin, and decreased calcium.

At the European Society for Medical Oncology Congress 2024, Nicolas Girard, MD, professor of respiratory medicine at Versailles Saint Quentin University, spoke to The American Journal of Managed Care^® (AJMC^®) about how the ADC improved patient-reported outcomes in the LUMINOSITY trial.⁴ Girard explained how patients who achieve stable disease during second-line treatment—not just those who show a significant response—can maintain their quality of life, physical function, and symptom control. This stability can lead to a longer period before quality of life deteriorates, consistent with previous findings.

“We see that this time is more prolonged in patients who are responders, and this is pretty expected—in all studies you have that,” Girard told AJMC. “But here we also have a more prolonged time to deterioration in patients with disease control, meaning including the patients with stable disease. So, for the patients, it's not only a matter of response, it's also a matter of stable disease, with a clear benefit in terms of quality of life to achieve in the second-line setting stable disease.”

Telisotuzumab vedotin is also being assessed as a monotherapy against docetaxel in patients with previously treated c-Met–overexpressing NSCLC in the TeliMET NSCLC-01 randomized phase 3 global study (NCT04928846), with enrollment underway at the time of publication.⁵ According to Girard, it will be important to monitor and proactively manage the adverse effects of this newly approved drug in the TeliMET trial and other future studies.⁴

“Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s),” the news release said.

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. AbbVie. News release. 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. Caffrey M. ADC improvements mean more targets, new questions about sequencing. AJMC. June 10, 2024. Accessed May 14, 2025. https://www.ajmc.com/view/adc-improvements-mean-more-targets-new-questions-about-sequencing
3. Study of Telisotuzumab Vedotin (ABBV-399) in Participants With Previously Treated c-Met+ Non-Small Cell Lung Cancer. https://clinicaltrials.gov/study/NCT03539536. Updated January 19, 2024. Accessed May 14, 2025.
4. McNulty R. Dr Nicolas Girard on LUMINOSITY: Teliso-V improves PROs in NSCLC. AJMC. September 16, 2024. Accessed May 14, 2025. https://www.ajmc.com/view/dr-nicolas-girard-on-luminosity-teliso-v-improves-pros-in-nsclc
5. A Study to Assess Disease Activity and Adverse Events of Intravenous (IV) Telisotuzumab Vedotin Compared to IV Docetaxel in Adult Participants With Previously Treated Non-Squamous Non-Small Cell Lung Cancer (NSCLC). https://clinicaltrials.gov/study/NCT04928846. Updated May 13, 2025. Accessed May 14, 2025.