The FDA has granted accelerated approval to lurbinectedin (ZepzelcaTM, Pharma Mar, S.A.) for adults with metastatic small-cell lung cancer (SCLC) experiencing disease progression on or after platinum-based chemotherapy.
The efficacy of lurbinectedin, a selective inhibitor of oncogenic transcription, was investigated in a multinational, single-arm, open-label phase 2 basket trial, PM1183-B-005-14 (Study B-005; NCT02454972), which enrolled adults with SCLC previously treated with only one chemotherapy-containing treatment at least three weeks prior to study initiation. In order to be eligible, patients needed to have an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or lower, measurable disease per Response Criteria in Solid Tumors (RECIST) version 1.1, adequate organ function, and no brain metastases. A total of 105 patients were treated with 3.2 mg/m2 lurbinectedin, administered as a one-hour intravenous infusion every three weeks until disease progression or unacceptable toxicity, for a primary end point of investigator-assessed overall response rate per RECIST 1.1.
Lurbinectedin resulted in an investigator-assessed overall response rate of 35%, with a median response duration of 5.3 months; per the independent review committee, the overall response rate was 30%, with a median duration of 5.1 months.
Adverse reactions occurring in at least 20% of patients included myelosuppression, fatigue, increased creatinine, 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 most frequent grade 3/4 adverse events of any cause included neutropenia, experienced by 46% of patients; leucopenia, experienced by 29%; anemia, experienced by 9%; and thrombocytopenia, experienced by 7%. Ten percent of patients experienced serious treatment-related adverse events, with neutropenia and febrile neutropenia being the most common (5% each). There were no treatment-related deaths.
"Lurbinectedin was active as second-line therapy for SCLC in terms of overall response and had an acceptable and manageable safety profile," wrote the investigators in their May publication in The Lancet Oncology, led by co-first authors José Trigo, MD, Phase 1 Trials Unit Director at the Hospital Universitario Virgen de la Victoria, Málaga, Spain, and Vivek Subbiah, MD, Center Clinical Medical Director of the Clinical Center for Targeted Therapy, Cancer Medicine division, at The University of Texas MD Anderson Cancer Center in Houston. "Lurbinectedin could represent a potential new treatment for patients with SCLC, who have few options especially in the event of a relapse, and is being investigated in combination with doxorubicin as second-line therapy in a randomized phase 3 trial."
The recommended dosage is 3.2 mg/m2 every 21 days. As with all accelerated approvals, continued approval may depend on verification and description of clinical benefit in confirmatory trials.
For More Information
Trigo J, Subbiah V, Besse B, et al (2020). Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol, 21(5):645-654. DOI:10.1016/S1470-2045(20)30068-1
ZepzelcaTM (lurbinectedin) prescribing information (2020). Jazz Pharmaceuticals, Inc., under license from Pharma Mar, S.A. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213702s000lbl.pdf
US Food and Drug Administration (2020). FDA grants accelerated approval to lurbinectedin for metastatic small cell lung cancer. Available at: https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-lurbinectedin-metastatic-small-cell-lung-cancer
Image credit: Ed Uthman. Licensed under CC BY 2.0