On June 15, 2020, the FDA accelerated the approval of lurbinectedin (Zepzelca; Jazz Pharma/Pharma Mar), an intravenous alkylating drug, for the treatment of adults with metastatic small-cell lung cancer (SCLC) that has progressed during or after platinum-based chemotherapy. Lurbinectedin represents a new mechanism of action that triggers a cascade of events involving DNA-binding proteins and DNA repair pathways that lead to the disruption of the natural cell cycle and eventual apoptosis. The FDA granted lurbinectedin an orphan drug designation and used its priority review for this indication.
“Seeing first-hand the aggressive nature of SCLC, and knowing that the large majority of those diagnosed will experience relapse, I am excited to see an effective new treatment demonstrating durable responses,” said William Jeffery Petty, MD, Professor, Hematology and Oncology, Wake Forest School of Medicine, in a Jazz Pharma press release. “For doctors, patients and their families, Zepzelca is an important and much-needed addition to the treatment landscape for relapsing SCLC.”
“The availability of Zepzelca presents new hope for patients and their loved ones, and we’re eager to see its impact on the SCLC community,” said Andrea Stern Ferris, President and CEO of LUNGevity, in the press release.
The FDA approved lurbinectedin for metastatic SCLC based on the results of the PM1183-B-005-14 clinical trial, a multicenter open-label, multicohort study of 105 patients with metastatic SCLC whose disease progressed during or after platinum-based chemotherapy. Patients received lurbinectedin 3.2 mg/m2 by intravenous infusion every 21 days until disease progression or unacceptable toxicity.
The main end points were confirmed overall response rate (ORR) by investigator assessment using RECIST 1.1 criteria and response duration. Among the 105 patients, the ORR was 35% (95% confidence interval [CI], 26%-45%), with a median response duration of 5.3 months (95% CI, 4.1-6.4). The ORR, as determined by independent review committee, was 30% (95% CI, 22%-40%), with a median response duration of 5.1 months (95% CI, 4.9-6.4).
The most common (≥20%) adverse reactions were myelosuppression, fatigue, increased creatinine levels, increased alanine aminotransferase, increased glucose, nausea, decreased appetite, musculoskeletal pain, decreased albumin, constipation, dyspnea, decreased sodium, increased aspartate aminotransferase, vomiting, cough, decreased magnesium, and diarrhea.
The recommended dose for lurbinectedin is 3.2 mg/m2 every 21 days.
This indication is approved under accelerated approval based on ORR and duration of response. Continued approval may be contingent on clinical benefits in confirmatory clinical trials.