The FDA approved lurbinectedin combined with atezolizumab (±hyaluronidase) for maintenance treatment of ES-SCLC in patients whose disease hasn’t progressed after first-line platinum-based chemotherapy plus atezolizumab, representing the first maintenance therapy option in this setting. This approval, based on the IMforte trial showing a 2.6-month OS benefit (13.2 vs 10.6 months, HR 0.73, p=0.0174) and 3.3-month PFS improvement (5.4 vs 2.1 months, HR 0.54, p<0.0001), establishes a new standard of care for maintaining remission in ES-SCLC. The combination received priority review and orphan drug designation under Project Orbis international collaboration.
Drug Profile & Mechanism
- Lurbinectedin (Zepzelca): RNA polymerase II inhibitor targeting transcription in tumor cells, manufactured by Jazz Pharmaceuticals
- Atezolizumab (Tecentriq/Tecentriq Hybreza): PD-L1 immune checkpoint inhibitor, manufactured by Genentech
- Target Population: Adult patients with extensive-stage small cell lung cancer (ES-SCLC) completing first-line induction without disease progression
- Partnership: Jazz Pharmaceuticals and Genentech collaboration for combination maintenance therapy
Regulatory Milestone Details
- Approval Date: October 2, 2025
- Regulatory Pathway: Priority review under Project Orbis (FDA collaboration with Australia TGA, Health Canada, Israel MOH, and Switzerland Swissmedic)
- Supporting Evidence: IMforte trial (NCT05091567), randomized open-label phase study with 483 ES-SCLC patients
- Special Designations: Orphan drug designation for both lurbinectedin and atezolizumab; Assessment Aid utilized
- Efficacy Endpoints: Co-primary endpoints of overall survival (OS) and progression-free survival (PFS) per RECIST v1.1
Practice Implications
- Treatment Sequencing: Establishes maintenance therapy option following 4 cycles of atezolizumab-carboplatin-etoposide induction in responding/stable ES-SCLC patients
- Patient Selection: Applicable to patients with ES-SCLC who complete first-line therapy without progression
- Clinical Benefits: Substantial PFS extension (3.3 months) with meaningful OS benefit (2.6 months) in a disease with historically poor prognosis
- Safety Monitoring: Requires vigilance for myelosuppression, hepatotoxicity, extravasation, rhabdomyolysis (lurbinectedin) and immune-mediated adverse reactions (atezolizumab)
- Administration Options: Flexibility with IV atezolizumab or subcutaneous atezolizumab/hyaluronidase formulation
Development Status & Next Steps
- Current Status: Fully approved for maintenance treatment in ES-SCLC; prescribing information available on Drugs@FDA
- International Review: Ongoing regulatory reviews in Australia, Canada, Israel, and Switzerland through Project Orbis
- Dosing Regimens: Lurbinectedin 3.2 mg/m² IV every 21 days; atezolizumab 840 mg Q2W, 1200 mg Q3W, or 1680 mg Q4W IV; or atezolizumab/hyaluronidase 1875 mg/30,000 units SC Q3W
- Monitoring Requirements: Adverse event reporting through MedWatch (1-800-FDA-1088); Project Facilitate available for investigational access (240-402-0004)
- No Further Trials Required: Full approval granted based on IMforte results demonstrating statistically significant OS and PFS benefits
