FDA Approves Emrelis in Previously Treated, Advanced NSCLC

The United States Food and Drug Administration (FDA) has approved treatment with Emrelis for adult patients with previously treated, locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with high c-Met protein overexpression, according to a news release from AbbVie. High c-Met protein overexpression, in this case, is defined as 50% or more of tumor cells with strong (3+) staining as determined by an FDA-approved test.

Notably, this makes Emrelis the first and only antibody drug conjugate approved by the regulatory agency for patients with previously treated, advanced NSCLC who have high c-Met protein overexpression. This is important because these patients often have a poor prognosis and limited treatment options, according to the release.

“We have observed a paradigm shift in oncology in recent decades toward personalized, biomarker-driven therapeutics, allowing for better selection and optimized treatment outcomes,” Dr. Jonathan Goldman, stated in the press release. “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.”

Goldman is a professor of Medicine in the Hematology/Oncology Division; the director of Clinical Trials in Thoracic Oncology; and the associate director of Early Drug Development at UCLA Health; as well as the chair of University of California Lung Cancer Consortium

This accelerated approval from the regulatory agency was supported by data from the phase 2 LUMINOSITY study which aimed to characterize the efficacy and safety of Emrelis in patients with Met overexpressing advanced NSCLC. It was found that of the 84 patients with high c-Met protein overexpression who received Emrelis achieved a 35% overall response rate. Moreover, the duration of response in this patient population was 7.2 months.

Regarding safety, the most common side effects to treatment which occurred in 20% of patients or mere were peripheral neuropathy, fatigue, decreased appetite and peripheral edema. Grade 3 (severe) or 4 (life-threatening) laboratory abnormalities which occurred in 2% of patients or more included decreased lymphocytes, increased glucose, increased alanine aminotransferase, increased gamma glutamyl transferase, decreased phosphorus, decreased sodium, decreased hemoglobin and decreased calcium.

“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.”

More Information on the LUMINOSITY Trial

Because nearly 85%% of lung cancers are classified as NSCLC, it is an extremely prevelant form of lung cancer. Despite this, the disease remains the leading cause of cancer-related deaths throughout the world. It is because of these unmet needs that investigators sought to evaluate new treatment options within this patient population.

In approximately 25% of patients with advanced EGFR wild type, non-squamous NSCLC, the c-Met protein is found to be overexpressed, leading to poor prognosis. Emrelis is a c-Met-directed antibody-drug conjugate which is designed to target the unique biomarkers and potently deliver a payload directly to the biomarker-expressing cell.

The phase 2 LUMINOSITY trial is an currently evaluating Emrelis. LUMINOSITY is identifying target NSCLC populations with c-Met overexpression that are most appropriate for the investigative therapy in the second- or third-line setting. The end points of the trial include overall response rate, duration of response, disease control rate and progression-free survival, as well as with overall survival.

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

Notably, this FDA accelerated approval comes after the FDA granted Emrelis breakthrough therapy designation in December of 2021, based on the phase 2 LUMINOSITY data.

Emrelis is now being investigated as a monotherapy in a the randomized, global, confirmatory phase 3 TeliMET NSCLC-01 study for people with previously treated c-Met overexpressing NSCLC. Enrollment is currently ongoing across global clinical trial sites.

Ongoing approval for this indication may depend on confirmation of clinical benefit in additional confirmatory trials, the news release concluded.

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