FDA Approves Lurbinectedin for Metastatic Small Cell Lung Cancer


The FDA has approved lurbinectedin (Zepzelca) for the treatment of adult patients with metastatic small cell lung cancer with disease progression, following platinum-based chemotherapy.

The FDA has approved lurbinectedin (Zepzelca) for the treatment of adult patients with metastatic small cell lung cancer with disease progression, following platinum-based chemotherapy, according to PharmaMar and Jazz Pharmaceuticals plc.1

The agent was approved under the FDA's "Accelerated Approval" Program, which allows for the conditional approval of a therapy that fills an unmet need for a serious or life-threatening disease or condition.

"It is great to see a new therapeutic agent available for patients with relapsed SCLC," said Charles M. Rudin, chief of the Thoracic Oncology Service at Memorial Sloan Kettering Cancer Center and principal investigator of the National Cancer Institute Small Cell Lung Cancer Consortium in a press release. "Lurbinectedin is the first new drug approved for second line treatment since 1996. SCLC remains a major unmet medical need. Many of us in the oncology community will welcome lurbinectedin as a new standard option for patients with recurrent SCLC."

The regulatory decision is based on data reported from an open-label, single-arm, phase 2 basket trial (NCT-2454972) of 105 patients with SCLC who have progressed on platinum-containing therapy.

Results from the trial showed that treatment with lurbinectedin led to an overall response rate (ORR) of 35.2% in these patients.2 The ORR was comprised of partial responses (PRs), which were experienced in 37 of 105 patients. An additional 35 patients achieved stable disease, translating to a disease control rate of 68.6% (95% CI, 58.8%-77.3%).

A median duration of response (DOR) of 5.3 months (95% CI, 4.1-6.4) was reported with lurbinectedin per investigator assessment. By independent review committee, the ORR with the agent was 30% and the DOR was 5.1 months.

For the trial, patients were recruited from 26 hospitals in 6 European countries as well as the United States. Patients aged ≥18 years with a pathologically-confirmed diagnosis of SCLC and an ECOG performance status of 2 or lower were eligible for enrollment. Patients also had to have measurable disease per RECIST v. 1.1, absence of brain metastases, adequate organ function, and had to have received only 1 previous line of chemotherapy a minimum of 3 weeks prior to the start of the study.

Patients in the SCLC cohort were enrolled between October 2015 and October 2018.3 The median age of participants was 60 years, with 35.2% of patients aged ≥65 years. Approximately 36% of patients had an ECOG performance score of 0; 56.2% had a score of 1, and 7.6% had a score of 2.

Patients had received a median of 1 prior lines of therapy. With regard to response to prior platinum-based therapy, 8.6% of patients had achieved a complete response, while 66.7% had experienced a PR. Moreover, 57% (n = 60) of patients had platinum-sensitive disease and 43% (n = 45) of patients had platinum-resistant disease.

Participants received 3.2 mg/m2 of lurbinectedin as a 1-hour intravenous infusion once every 3 weeks until either progressive disease or unacceptable toxicity.

The primary end point of the trial was the proportion of patients with an overall response per investigator assessment according to RECIST v 1.1 criteria. All patients who received treatment with the agent were evaluated for efficacy and safety.

Additional results showed that the majority of the patients, or 65%, experienced a reduction in tumor size. Notably, responses were reported in 5 of 8 patients in whom prior immunotherapy had failed. A total of 28 patients, or 26.7%, experienced disease progression and 5 patients were not evaluable.

Earlier results showed that response rates with lurbinectedin were higher in patients with platinum-sensitive disease. Of those patients, the ORR was 45% versus just 22.2% in those with platinum-resistant disease.

The median progression-free survival (PFS) was 3.9 months months (95% CI, 2.6-4.6) and the 6-month PFS rate was 33.6% (95% CI, 24.0-43.1). In those with platinum-sensitive disease, 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 those with platinum-resistant disease, 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 with lurbinectedin was 9.3 months (95% CI, 6.3-11.8); the 12-month OS rate was 34.2% (95% CI, 23.2-45.1). In patients who were platinum sensitive, the median OS was 11.9 months versus 5.0 months patients who were platinum resistant.

With regard to safety, all-grade adverse events (AEs) were reported in 84.8% of patients. The most common grade 1/2 AEs reported included fatigue (51.4%), nausea (32.4%), decreased appetite (21.0%), vomiting (18.1%), diarrhea (12.4%), constipation (9.5%), and neutropenia (5.7%).

A total of 34.3% of patients reported a grade ≥3 AE. The most commonly reported grade 3/4 AEs were hematologic abnormalities, including anemia (9%), leucopenia (29%), neutropenia (46%), and thrombocytopenia (7%).

Serious treatment-related AEs were reported in 10.5% of patients. Of these events, neuropenia and febrile neutropenia were the most common events reported (5%, each).

Discontinuations, dose delays, and dose reductions, related to AEs were reported in 1.9%, 22.1%, and 26.3% of patients, respectively. No AE-related deaths were reported.

The approval will permit Jazz Pharmaceuticals to make lurbinectedin commercially available in the United States in early July 2020.

“Small cell lung cancer is a disease with limited treatment options, and the approval of lurbinectedin represents an important advance for patients whose metastatic SCLC has progressed after platinum-based therapy,” said Bruce Cozadd, chairman and CEO of Jazz Pharmaceuticals in the press release.

“While patients may initially respond to traditional chemotherapy, they often experience an aggressive recurrence that is historically resistant to treatment," Cozadd added. "Jazz congratulates PharmaMar on the successful development of lurbinectedin and we are proud to partner with them to bring this new therapy to the US market, expanding our presence in oncology.”


  1. PharmaMar announces the US FDA approval of lurbinectedin (Zepzelca) for the treatment of metastatic small cell lung cancer. News release. June 15, 2020. Accessed June 15, 2020.
  2. Trigo J, Subbiah V, Besse B, et al. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020;21(5):645-654. doi:10.1016/S1470-2045(20)30068-1
  3. 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.
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