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The FDA has granted a priority review designation to a new drug application for lurbinectedin as a treatment for patients with small cell lung cancer who have progressed following platinum-containing therapy.
The FDA has 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.1
The designation is based on findings from a phase II basket trial (NCT02454972), in which lurbinectedin elicited a 35.2% overall response rate (ORR) in this patient population.2 The ORR consisted of all partial responses (PRs), which occurred 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.
Under the Prescription Drug User Fee Act, the FDA is expected to make a decision on the NDA by August 16, 2020.
Topotecan has been the only FDA-approved, second-line therapy for patients with platinum-sensitive SCLC. Historical response rates with the agent in this setting range from 5% to 24%, with a median overall survival (OS) of 6 to 8 months.
Lurbinectedin inhibits RNA polymerase II, and by blocking trans-activated transcription, it induces apoptosis. Prior research demonstrated strong clinical activity with lurbinectedin when used in combination with doxorubicin in the second-line setting for patients with SCLC, particularly in those with platinum sensitivity.
In the multicenter, single-arm, phase II basket study, investigators evaluated the safety and efficacy of lurbinectedin in patients across advanced several solid tumors, including SCLC.
The 105 patients in the SCLC cohort were enrolled between October 2015 and October 2018. The median patient age was 60 years (range, 40-83) and 35.2% of patients were aged ≥65 years. The ECOG performance status was 0 for 36.2% of patients, 1 for 56.2% of patients, and 2 for 7.6% of patients.
The median number of prior therapies was 1 (range, 1-2). Regarding response to prior platinum-based therapy, 8.6% of patients had a complete response and 66.7% of patients had a PR. Fifty-seven percent (n = 60) of patients had sensitive disease and 43% (n = 45) of patients had resistant disease.
Patients received 3.2 mg/m2 of lurbinectedin as a 1-hour intravenous infusion once every 3 weeks. At the time of the data cutoff, 11 patients remained on treatment, 25 patients had discontinued treatment, 66 patients had died, and 3 were lost to follow-up.
Additional results showed that 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, defined as those with a chemotherapy-free interval (CTFI) ≥90 days. Among these patients, the ORR was 45% compared with 22.2% in patients with resistant disease (CTFI <90 days).
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 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.
Regarding safety, all-grade adverse events (AEs) occurred in 84.8% of patients, with 34.3% of patients experiencing a grade ≥3 AE. Serious AEs were observed in 10.5% of patients. AE-related discontinuations, dose delays, and dose reductions, occurred in 1.9%, 22.1%, and 26.3% of patients, respectively. There were no AE-related deaths.
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%), increased alanine aminotransferase level (1.9%), skin ulcer (1.0%), and diarrhea (1.0%).