The FDA granted a priority review designation to a new drug application (NDA) for lurbinectedin as a treatment for patients with small cell lung cancer (SCLC) who have progressed following platinum-containing therapy, according to PharmaMar and Jazz Pharmaceuticals.1
The FDA has set a PDUFA target action date of August 16, 2020.
The designation is based on findings from a multicenter, single-arm phase II basket trial, designed to evaluate the safety and efficacy of lurbinectedin in patients across advanced several solid tumors, including SCLC.2
Treatment with lurbinectedin induced a 35.2% overall response rate (ORR), which consisted of all partial responses (PRs) occurring in 37 of 105 patients. An additional 35 patients had stable disease, leading to a disease control rate of 68.6% (95% CI, 58.8%-77.3%).
Overall, 65% of patients had a decrease in tumor size and responses occurred in 5 of 8 patients who had failed prior immunotherapy. Twenty-eight patients (26.7%) had progressive disease and 5 patients were not evaluable.
The median duration of response was 5.3 months (95% CI, 4.1-6.4). The response rate was higher in patients with platinum-sensitive disease, wherethe ORR was 45% compared with 22.2% in patients with resistant disease.
Overall, the median progression-free survival (PFS) was 3.9 months (95% CI, 2.6-4.6) and the 6-month PFS rate was 33.6% (95% CI, 24.0-43.1). In the sensitive subgroup, the median PFS was 4.6 months (95% CI, 3.0-6.5) and the 6-month PFS rate was 44.6% (95% CI, 31.2-57.9). In the resistant population, the median PFS was 2.6 months (95% CI, 1.3-3.9) and the 6-month PFS rate was 18.8 months (95% CI, 6.8-30.9).
At a median follow-up of 17.1 months, the median overall survival (OS) was 9.3 months (95% CI, 6.3-11.8) and the 12-month OS rate was 34.2% (95% CI, 23.2-45.1). The median OS was 11.9 months in sensitive patients versus 5.0 months in resistant patients.
The most common grade 1/2 adverse events (AEs) included fatigue (51.4%), nausea (32.4%), decreased appetite (21.0%), vomiting (18.1%), diarrhea (12.4%), constipation (9.5%), and neutropenia (5.7%). Grade 3/4 AEs included neutropenia (22.9%), anemia (6.7%), fatigue (6.7%), thrombocytopenia (4.8%), febrile neutropenia (4.8%), pneumonia (1.9%), increased alanine aminotransferase level (1.9%), skin ulcer (1.0%), and diarrhea (1.0%).
1. PharmaMar and Jazz Pharmaceuticals Announce FDA Acceptance and Priority Review of New Drug Application for Lurbinectedin in Relapsed Small Cell Lung Cancer [news release]: Madrid, Spain and Dublin, Ireland. PharmaMar (MSE:PHM) and Jazz Pharmaceuticals plc. Published February 17, 2020. https://www.prnewswire.com/news-releases/pharmamar-and-jazz-pharmaceuticals-announce-fda-acceptance-and-priority-review-of-new-drug-application-for-lurbinectedin-in-relapsed-small-cell-lung-cancer-301005785.html. Accessed February 17, 2020.
2. Paz-Ares LG, Perez JMT, Besse B, et al. Efficacy and safety profile of lurbinectedin in second-line SCLC patients: Results from a phase II single-agent trial. J Clin Oncol. 2019;37(suppl; abstr 8506). doi: 10.1200/JCO.2019.37.15_suppl.8506.