PharmaMar Asks FDA for Accelerated Approval of Lurbinectedin to Treat Relapsed SCLC

PharmaMar is asking the U.S. Food and Drug Administration (FDA) to approve lurbinectedin (PM1183) to treat those with small cell lung cancer (SCLC) whose disease progressed following platinum-based chemotherapy.

The new drug application (NDA) requesting accelerated approval for lurbinectedin was based on data from a multicenter, open-label Phase 2 trial (NCT02454972), where lurbinectedin was found to be active, safe, and to lead to promising treatment responses when used alone as a second-line therapy in people with SCLC.

Accelerated approval is a form of conditional approval given to a medication that addresses an unmet need in a serious medical condition, providing it has shown benefits on surrogate or interim measures in a clinical trial. A confirmatory study will be needed for full approval to be given.

Relapsed SCLC falls within this “unmet need” category, with the most recent treatment for relapsed SCLC being the chemotherapy agent topotecan, which the FDA approved in 1996.

“The application for registration under accelerated approval regulations gives us the possibility that the FDA could approve lurbinectedin in the U.S. for treatment of small cell lung cancer in 2020 and that, if approval is obtained, could begin to be marketed in the second half of 2020,” Luis Mora, general manager of PharmaMar’s Oncology Business Unit, said in a press release.

Lurbinectedin is an inhibitor of RNA polymerase, an enzyme that is overactive in many types of solid tumors and plays a key role in protein production.

By interrupting the process, lurbinectedin is designed to prevent cancer cells from making proteins they need to survive, and to stop the secretion of pro-tumoral molecules by certain immune cells, eventually killing cancer cells.

Data from the Phase 2 trial that supported the NDA application was in the oral presentation, “Efficacy and safety profile of lurbinectedin in second-line SCLC patients: Results from a phase II single-agent trial,” given at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting, in Chicago.

The study enrolled 105 people with relapsed SCLC at 39 sites across the U.S. and Europe.

Its main goal was at least 30% of patients attaining a complete or partial response to treatment with lurbinectedin, collectively known as an overall response rate (ORR). Complete and partial responses mean that the cancer has either been fully or partly eliminated.

Additional goals included measures of the duration of treatment response, overall survival (OS), and the time until disease progression (progression-free survival, or PFS).

Study findings, also detailed and updated in a news release, showed the trial met its primary endpoint, with 35.2% of overall patients responding to treatment.

Responses, however, were particularly better among people with platinum-sensitive disease — a 45% ORR — or those who initially responded to chemotherapy but later relapsed. Patients with platinum-resistant disease — meaning a relapse soon after a first-line chemotherapy — had a response rate of 22.2%.

In the trial’s overall population, the median duration of response was 5.3 months. These were also slightly higher among those with sensitive disease (6.2 months), and slightly lower for those with resistant disease (4.7 months).

The same trends were seen for OS and PFS, with patients with sensitive disease living longer and experiencing signs of disease progression later (OS of 11.9 months, and PFS of 4.6 months) than those with resistant disease (OS of 5.0 months, and PFS of 2.6 months). The median OS and PFS in the overall population of patients in the study was 9.3 and 3.9 months, respectively.

“It is great to finally see some new therapeutic options arriving for small cell lung cancer patients, who represent a major unmet medical need,” said Charles Rudin, MD, PhD, chief of the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center and principal investigator of the NCI Small Cell Lung Cancer Consortium.

“I have been following the emerging clinical trial data on lurbinectedin, which suggest appealing efficacy and a tolerable safety profile. I believe many treating physicians may welcome lurbinectedin, if approved, as a new standard of care option for their patients with recurrent small cell lung cancer,” Rudin added.

Lurbinectedin had a favorable and manageable safety profile. The most common treatment-related adverse effects reported included low white blood cell counts, nausea or vomiting and fatigue.

Severe (grade 3) or life-threatening (grade 4) events included neutropenia, or low neutrophil levels, (22.9%), febrile neutropenia (4.8%), anemia (6.7%) and low platelet counts (4.8%).

“These results demonstrate that lurbinectedin is a strong candidate to become a therapeutic alternative for patients with small cell lung cancer, a large unmet medical need,” José María Fernández, president of PharmaMar, said in the news release.