On May 14, the Food and Drug Administration (FDA) granted accelerated approved of Emrelis (telisotuzumab vedotin) for certain people with advanced or metastatic lung cancer based on a study showing an overall response rate of 35%.
Emrelis, from AbbVie, is a novel antibody-drug conjugate (ADC). It consists of an antibody that targets c-MET, a receptor tyrosine kinase that promotes cell growth, coupled with a topoisomerase inhibitor chemotherapy drug. ADCs deliver their toxic payload directly to tumors, reducing collateral damage to healthy cells.
Specifically, the accelerated approval is for previously treated patients with locally advanced or metastatic non-squamous non-small-cell lung cancer (NSCLC) with high c-Met protein overexpression, as determined by an FDA-approved test. Around 25% of people with advanced EGFR wild-type NSCLC (meaning it lacks mutations that make it treatable with EGFR inhibitors) show c-Met protein overexpression, and about half of those have high c-Met overexpression on at least 50% of tumor cells, according to AbbVie.
“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, of the University of California Los Angeles, said in an AbbVie news 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.”
The approval is supported by findings from the Phase II LUMINOSITY trial (NCT03539536), which included 84 people with EGFR wild-type NSCLC who had previously been treated with at least one prior systemic therapy.
The study participants received Emrelis via IV infusion every two weeks until disease progression or unacceptable toxicity. All patients in this open-label study were treated with Emrelis, and there was no placebo or comparison regimen control group.
The overall response rate, indicating tumor shrinkage, was 35%, and the median duration of response was 7.2 months. Therapies that received accelerated approval based on these endpoints must undergo further testing to determine if they offer clinical benefits, such as improved survival, and the FDA can pull drugs that fail to measure up.
Treatment was generally safe, though side effects were common. While ADCs deliver chemotherapy directly to tumors, the highly toxic medications still take their toll. The most frequently reported adverse reactions affecting at least 20% of patients were peripheral neuropathy, fatigue, decreased appetite and swelling. The most common severe (Grade 3 or 4) laboratory abnormalities included decreased lymphocytes, decreased hemoglobin, increased glucose and elevated liver enzymes.
Emrelis is now being further evaluated in a global randomized Phase III confirmatory trial called TeliMET NSCLC-01 (NCT04928846).
“Despite the progress we have seen in the treatment of lung cancer, we need more options for people whose treatments stop working,” said LUNGevity Foundation executive director Upal Basu Roy, PhD, MPH. “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.”
Click here for full prescribing information for Emrelis.
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