FDA Approves Lurbinectedin for Metastatic Small Cell Lung Cancer

June 16, 2020

The FDA approved lurbinectedin for the treatment of adult patients with metastatic small cell lung cancer under accelerated approval based on overall response rate and duration of response in a phase 2 study.

The FDA has approved lurbinectedin (Zepzelca) for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy, according to Jazz Pharmaceuticals along with its partner PharmaMar.1

The agent was approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR) from a phase 2 study; however, continued approval for this indication may be dependent upon verification and description of clinical benefit in a confirmatory trial.

"Seeing first-hand the aggressive nature of SCLC and knowing that the large majority of those diagnosed will experience relapse, I am excited to see an effective new treatment demonstrating durable responses," Jeff Petty, MD, oncology specialist at Wake Forest Baptist Health, said in a press release. "For doctors, patients and their families, (lurbinectedin) is an important and much-needed addition to the treatment landscape for relapsing SCLC."

Lurbinectedin was approved by the FDA based on monotherapy clinical data from an open-label, multi-center, single-arm, phase 2 study of 105 adult patients with SCLC who were platinum-sensitive and platinum-resistant with disease progression after treatment with platinum-based chemotherapy. In the trial, patients were treated with 3.2 mg/m2 of lurbinectedin, administered as a 60-minute intravenous (IV) infusion repeated every 21 days until disease progression or unacceptable toxicity.

The data showed that in patients with relapsed SCLC, lurbinectedin demonstrated an ORR of 35% and a median DOR of 5.3 months as measured by investigator assessment, and 30% and 5.1 months, respectively, as measured by an independent review committee.

Lurbinectedin was discontinued in 1.9% of patients and was delayed in 30.5% of patients due to an adverse reaction. Further, dose reductions due to an adverse reaction occurred in 25% of patients.

The most common grade 3/4 adverse events (AEs) were hematological abnormalities – specifically, anemia (9%), leucopenia (29%), neutropenia (46%), and thrombocytopenia (7%).2 Serious treatment-related AEs were reported in 11 (10%) patients, of which neutropenia and febrile neutropenia were the most common (5% each). No treatment-related deaths were reported.

"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 on or after platinum-based therapy," Bruce Cozadd, chairman and CEO of Jazz Pharmaceuticals, said in the release. "While patients may initially respond to traditional chemotherapy, they often experience an aggressive recurrence that is historically resistant to treatment. 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."

Administered by IV infusion, the current recommended dose of lurbinectedin is 3.2 mg/m2 over the course of 1 hour, repeated every 21 days until disease progression or unacceptable toxicity. Notably, lurbinectedin can be administered in an outpatient clinic and its dosing schedule may result in patients spending less time on treatment in the clinic or hospital compared to other options.

Starting in early July, lurbinectedin will be commercially available in the US.

Reference:

1. Jazz Pharmaceuticals Announces U.S. FDA Accelerated Approval of Zepzelca™ (lurbinectedin) for the Treatment of Metastatic Small Cell Lung Cancer [news release]. Dublin. Published June 15, 2020. finance.yahoo.com/news/jazz-pharmaceuticals-announces-u-fda-193500368.html. 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. The Lancet Oncology. doi:10.1016/S1470-2045(20)30068-1.