FDA Grants Accelerated Approval to Lurbinectedin for Metastatic Small Cell Lung Cancer

June 15, 2020

The following is a message from the Director of the FDA Oncology Center of Excellence, Dr. Richard Pazdur:

On June 15, 2020, the Food and Drug Administration granted accelerated approval to lurbinectedin (ZEPZELCA, Pharma Mar S.A.) for adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy.

Efficacy was demonstrated in the PM1183-B-005-14 trial (Study B-005; NCT02454972), a multicenter open-label, multi-cohort study enrolling 105 patients with metastatic SCLC who had disease progression on or after platinum-based chemotherapy. Patients received lurbinectedin 3.2 mg/m2 by intravenous infusion every 21 days until disease progression or unacceptable toxicity.

The main efficacy outcome measures were confirmed overall response rate (ORR) determined by investigator assessment using RECIST 1.1 and response duration. Among the 105 patients, the ORR was 35% (95% CI: 26%, 45%), with a median response duration of 5.3 months (95% CI: 4.1, 6.4). The ORR as per independent review committee was 30% (95% CI: 22%, 40%) with a median response duration of 5.1 months (95% CI: 4.9, 6.4).

The most common adverse reactions (≥20%), including laboratory abnormalities, were myelosuppression, fatigue, increased creatinine, increased alanine aminotransferase, increased glucose, nausea, decreased appetite, musculoskeletal pain, decreased albumin, constipation, dyspnea, decreased sodium, increased aspartate aminotransferase, vomiting, cough, decreased magnesium and diarrhea.

The recommended lurbinectedin dose is 3.2 mg/m2 every 21 days.

View full prescribing information for ZEPZELCA.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this application, a modified Project Orbis was undertaken because of the timing of submission to other regulatory agencies. FDA is collaborating with the Australian Therapeutic Goods Administration (TGA). FDA approved this application 2 months ahead of the goal date. The review is ongoing for the Australian TGA.

FDA granted lurbinectedin orphan drug  designation for the treatment of SCLC and priority review to this application. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.

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