FDA Grants Accelerated Approval to Telisotuzumab Vedotin In Pretreated Advanced NSCLC With c-MET Overexpression

FDA

The FDA has granted accelerated approval to telisotuzumab vedotin-tllv (Emrelis) for the treatment of adult patients with locally advanced or metastatic, nonsquamous non–small cell lung cancer (NSCLC) harboring high c-MET protein overexpression who have received a prior systemic therapy.1

High c-MET protein overexpression is defined as strong (immunohistochemistry [IHC] 3+) staining on at least 50% of tumor cells, based on an FDA-approved test. In conjunction with the approval of telisotuzumab vedotin, the FDA approved Roche's VENTANA MET (SP44) RxDx Assay as an IHC companion diagnostic to identify patients who may be eligible for treatment with the antibody-drug conjugate (ADC).

The regulatory decision was supported by data from the phase 2 LUMINOSITY trial (NCT03539536), which showed that patients with high c-MET protein overexpression treated with telisotuzumab vedotin (n = 84) achieved an overall response rate (ORR) of 35% (95% CI, 24%-46%) and a median duration of response (DOR) of 7.2 months (95% CI, 4.2-12).1,2 All responses were partial responses; the 6- and 12-month DOR rates were 59% and 21%, respectively.

"We have observed a paradigm shift in oncology in recent decades toward personalized, biomarker-driven therapeutics, allowing for better selection and optimized treatment outcomes," Jonathan Goldman, MD, professor of medicine and director of Thoracic Oncology Clinical Trials at UCLA, stated in a news release. "People with c-MET overexpressing NSCLC have poor prognosis and limited treatment options, and [telisotuzumab vedotin] is a first-in-class ADC that can address a critical unmet need for this patient population."

Looking at LUMINOSITY: Design, Treatment, Objectives

LUMINOSITY was an open-label, single-arm trial that enrolled patients at least 18 years of age with locally advanced or metastatic NSCLC with confirmed high c-MET overexpression per IHC testing.3 Patients also needed to have nonsquamous and EGFR wild-type disease. Notably, patients with other actionable mutations were allowed to enroll in part 1 if EGFR status was known; part 2 was limited to patients with nonsquamous, EGFR wild-type disease.

Patients needed to have disease progression following or intolerabilty to systemic cytotoxic therapy; an immune checkpoint inhibitor with or without chemotherapy; and prior targeted anticancer therapies if indicated. No more than 2 prior lines of systemic therapy—including 1 line of chemotherapy—were allowed in the locally advanced or metastatic setting; however, multiple lines of TKIs counted as 1 line of therapy.

An ECOG performance status of 0 or 1 was also required. Patients with central nervous system metastases were allowed to enroll after definitive therapy.

All patients received telisotuzumab vedotin at 1.9 mg/kg once every 2 weeks.2,3 ORR and safety served as the trial's primary end points. Secondary end points included DOR, disease control rate, progression-free survival, and overall survival.3

Patient Characteristics

Enrolled patients had a median age of 64 years (range, 38-83), and the majority were male (75%) and White (61%).2 Additionally, 74% of patients had an ECOG performance status of 1. Nineteen percent of patients were never smokers, 68% were former smokers, and 13% were current smokers. Stage IV disease was the most prominent (99%), and 19% of patients had previously treated brain metastases.

Patients received a median of 1 prior line of therapy (range, 1-3). Patients received either 1 (73%) 2 (24%), or 3 (3.6%) prior lines of systemic therapy. Prior systemic therapy included platinum-based chemotherapy (96%), immunotherapy (82%), targeted therapy (6%), and MET TKI (3.6%).

Safety Spotlight

Regarding safety, the most common adverse effects that occurred in at least 20% of patients treated with telisotuzumab vedotin during LUMINOSITY included peripheral neuropathy, fatigue, decreased appetite, and peripheral edema.1

The most common grade 3/4 laboratory abnormalities occurring in at least 2% of patients consisted of decreased lymphocyte count, increased glucose level, increased alanine aminotransferase level, increased gamma glutamyl transferase level, decreased phosphorus level, decreased sodium level, decreased hemoglobin level, and decreased calcium level.

"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 LUNGevity Foundation, added in a news release.1 "This approval is a welcomed targeted therapy for those with high c-MET protein overexpressing late-stage, NSCLC who have seen very limited treatment innovation in the last decade."

Looking Ahead

Telisotuzumab vedotin is being further evaluated in the phase 3 TeliMET NSCLC-01 trial (NCT04928846), where patients with previously treated, advanced nonsquamous NSCLC are being randomly assigned to receive the ADC or docetaxel.4

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. Emrelis. Prescribing information. AbbVie. May 2025. Accessed May 14, 2025. https://www.rxabbvie.com/pdf/emrelis_pi.pdf
3. Study of telisotuzumab vedotin (ABBV-399) in participants with previously treated c-Met+ non-small cell lung cancer. ClinicalTrials.gov. Updated January 19, 2024. Accessed May 14, 2025. https://clinicaltrials.gov/study/NCT03539536
4. 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). ClinicalTrials.gov. Updated May 13, 2025. Accessed May 14, 2025. https://clinicaltrials.gov/study/NCT04928846