On 15 June 2020, the US Food and Drug Administration (FDA) 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 multicentre 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 v1.1 and response duration.
Among the 105 patients, the ORR was 35% (95% confidence interval [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, dyspnoea, decreased sodium, increased aspartate aminotransferase, vomiting, cough, decreased magnesium and diarrhoea.
The recommended lurbinectedin dose is 3.2 mg/m2 every 21 days.
Full prescribing information for ZEPZELCA is available here.
This indication is approved under accelerated approval based on ORR 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’s 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.
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.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.