FDA to Accelerate the Approval of Lurbinectedin in Small Cell Lung Cancer

The FDA has granted Priority Review to the New Drug Application (NDA) for lurbinectedin, which is being considered for accelerated approval as a treatment of patients with small cell lung cancer (SCLC) who have progressed after prior platinum-containing therapy.

The NDA was based on data from the phase II basket trial, which were presented at the 2019 ASCO Annual Meeting.

In the study, second-line lurbinectedin demonstrated an overall response rate (ORR) of 35.2%, which included partial responses (PRs) in 37 of the 105 patients, and 35 cases of stable disease (SD). The disease control rate was 68.6% (95% CI, 58.8%-77.3%). Tumor size decreased in 65% of patients overall and these responses included 5 out the 8 patients who failed prior immunotherapy. Progressive disease occurred in 26.7% of patients in the study.

The median duration of response (DOR) observed was 5.3 months (95% CI, 4.1-6.4). The responses were higher in patients with chemotherapy-free interval (CTF) &ge;90 days. Of those patients, the ORR was 45% compared with the 22.2% ORR observed in patients with resistant disease CTF <90 days.

Overall, the median progression-free survival (PFS) was 3.9 months (95% CI, 2.6-4.6). Patients with CTF &ge;90 days had a median PFS of 4.6 months (95% CI, 31.2%-57.9%), and those with resistant disease had a median PFS of 2.6 months (95% CI, 1.3-3.9). At 6 months, the median PFS for the overall population was 33.6% (95% CI, 24.0-43.1). For patients with CTF &ge;90 days, the median PFS at 6-months was (95% CI, 31.2%-57.9%) and for those with resistant disease, the median PFS was 18.8 months (95% CI, 6.8-30.9) at 6 months.

At a median follow-up of 17.1 months, patients had a median overall survival of 9.3 months (95% CI, 6.3-11.8) and the 12-month overall survival (OS) rate was 34.2% (95% CI, 23.2%-45.1%). In the subgroup of patients with CTF &ge;90 days, the median OS was 11.9 months and for patients with resistant disease, the median OS was 5.0 months.

Adverse events (AEs) occurred in 84.8% of patients, covering all grade levels. Grade 3 AEs occurred in 34.3% of patients and 10.5% of patients experienced serious AEs. The most common grade 1/2 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%), increase alanine aminotransferase level (1.9%), skin ulcer (1.0%), and diarrhea (1.0%).

Treatment was discontinued in 1.9% of the patients overall. Additionally. 22.1% of patients with grade 3 AEs and 26.3% of those with serious AEs discontinued treatment with lurbinectedin.

The primary end point was ORR and the secondary end points included DOR, PFS, and OS.

To be eligible to be included in the study, patients were required to be at least 18 years of age with a pathologically proven diagnosis of SCLC, an ECOG performance status of 0 to 2, and adequate major organ function. Individuals who had prior treatment with lurbinectedin or trabectedin, prior or concurrent malignant disease, or known central nervous system involvement were excluded from the study.

Now that the FDA has granted Priority Review to the NDA for lurbinectedin, a Prescription Drug User Fee Act (PDUFA) target action date has been set as August 16, 2020.

References

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: PharaMar and Jazz Pharmaceuticals; February 17, 2020. https://bit.ly/2wkdws1. 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).