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

AbbVie  announced that Emrelis (telisotuzumab vedotin-tllv) has been granted accelerated approval by the FDA for the treatment of adult patients with locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with high c-Met protein overexpression (OE) who have received a prior systemic therapy. High c-Met protein overexpression is defined as ≥ 50% of tumor cells with strong (3+) staining as determined by an FDA-approved test.

This indication is approved based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). Emrelis is a c-Met-directed antibody-drug conjugate (ADC) and the first and only treatment approved for this patient population. ADCs are designed to target unique biomarkers such as the c-Met protein and deliver a potent 'payload' directly to the biomarker-expressing cell.

The FDA accelerated approval is supported by data from the Phase II  LUMINOSITY study (NCT03539536), a study designed to characterize the efficacy and safety of Emrelis in c-Met overexpressing advanced NSCLC populations. Findings from the study showed patients with high c-Met protein overexpression (n=84) who received Emrelis demonstrated a 35% (95% CI: 24, 46) Overall Response Rate (ORR) and Duration of Response (DOR) with a median of 7.2 months (95% CI: 4.2, 12). The most common adverse reactions (≥20%) were peripheral neuropathy, fatigue, decreased appetite and peripheral edema. The most common Grade 3 or 4 lab abnormalities (≥2%) were decreased lymphocytes, increased glucose, increased alanine aminotransferase, increased gamma glutamyl transferase, decreased phosphorus, decreased sodium, decreased hemoglobin and decreased calcium. (see citation). 

 "We have observed a paradigm shift in oncology in recent decades toward personalized, biomarker-driven therapeutics, allowing for better selection and optimized treatment outcomes," said Prof. Jonathan Goldman, director of thoracic oncology clinical trials, UCLA. "People with c-Met overexpressing NSCLC have poor prognosis and limited treatment options, and EMRELIS is a first-in-class ADC that can address a critical unmet need for this patient population."

- Despite the progress we have seen in the treatment of lung cancer, we need more options for people whose treatments stop working," said Dr. Upal Basu Roy,  executive director of research, LUNGevity Foundation, a leading lung cancer nonprofit organization. "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."

The LUMINOSITY trial (NCT03539536) is an ongoing Phase II study designed to identify the target NSCLC populations that overexpress c-Met best suited for telisotuzumab vedotin-tllv monotherapy in the second-line or third-line setting, and then to expand the groups to further evaluate efficacy in the selected populations. The endpoints include overall response rate (ORR), duration of response (DOR), disease control rate (DCR) and progression-free survival (PFS) per independent central review (ICR) as well as overall survival (OS).

"Emrelis, 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," said Dr. Roopal Thakkar, executive vice president, research and development, chief scientific officer, AbbVie. "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."

See citation- Camidge DR,, Bar J, Horinouchi H, Goldman J 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, ;42:3000 doi: 10.1200/JCO.24.00720.  PMID: 38843488; PMCID: PMC11361350.