The Food and Drug Administration (FDA) has accepted for Priority Review the New Drug Application (NDA) for lurbinectedin (PharmaMar and Jazz Pharmaceuticals) for the treatment of patients with small cell lung cancer (SCLC) who have progressed after prior platinum-containing therapy.
Lurbinectedin is a selective inhibitor of trans-activated RNA polymerase II transcription. The investigational drug is believed to downregulate the production of cytokines associated with tumor growth by inhibiting oncogenic transcription in tumor-associated macrophages.
The application is supported by data from a multicenter, single-arm phase 2 study (NCT02454972) that evaluated the antitumor activity of lurbinectedin as a second-line treatment for patients with relapsed SCLC (N=105). Patients received 3.2mg/m2 of lurbinectedin as a 1 hour intravenous infusion every 3 weeks. The primary end point was the overall response rate (ORR), defined as the percentage of evaluable patients with either complete or partial responses.
Results demonstrated that lurbinectedin achieved the primary end point with an ORR of 35.2% (95% CI, 26.2-45.2) in the overall population, 45% (95% CI, 32.1-58.4) in patients with sensitive disease (CTFI ≥90 days, defined as those who suffer a relapse in ≥90 days) and 22.2% (95% CI, 11.2-37.1) in patients with resistant disease (CTFI <90 days, defined as those who suffer a relapse in <90 days). Additional secondary end points included the following data in the overall population, sensitive patients, and resistant patients, respectively:
- Disease Control Rate: 68.6% (95% CI, 58.8-77.3); 81.7% (95% CI, 69.6-90.5); 51.1% (95% CI, 35.8-66.3).
- Median Duration of Response: 5.3 months (95% CI, 4.1-6.4); 6.2 months (95% CI, 3.5-7.3); 4.7 months (95% CI, 2.6-5.6).
- Median Progression Free Survival: 3.9 months (95% CI, 2.6-4.6); 4.6 months (95% CI, 3.0-6.5); 2.6 months (95% CI, 1.3-3.9).
- Median Overall Survival (OS): 9.3 months (95% CI, 6.3-11.8); 11.9 months (95% CI, 9.7-16.2); 5.0 months (95% CI, 4.1-6.3).
With regard to safety, the most common treatment-emergent adverse events included neutropenia, nausea or vomiting, and fatigue.
A Prescription Drug User Fee Act (PDUFA) target date of August 16, 2020 has been set for this application.