FDA Approval of Zepzelca® (Lurbinectedin) Plus Tecentriq® (Atezolizumab) for Extensive-Stage Small Cell Lung Cancer

Regulatory Decision

On October 3, 2025, the U.S. FDA approved the combination of Zepzelca® (lurbinectedin, Jazz Pharmaceuticals) and Tecentriq® (atezolizumab, Roche/Genentech) for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) who have not received prior systemic therapy. This marks the first immunotherapy-chemotherapy combination incorporating lurbinectedin to enter the frontline ES-SCLC setting.

Background on the Drugs

• Lurbinectedin (Zepzelca): Approved by the FDA in June 2020 under accelerated approval as monotherapy for adult patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy.
• Atezolizumab (Tecentriq): Approved by the FDA in May 2016 for urothelial carcinoma and subsequently expanded to multiple indications including non-small cell lung cancer (NSCLC), triple-negative breast cancer (TNBC), hepatocellular carcinoma (HCC), and in March 2019 as the first immunotherapy approved in combination with carboplatin and etoposide for first-line ES-SCLC.

Regulatory Pathway

This approval was based on a supplemental New Drug Application (sNDA) filed by Jazz Pharmaceuticals for lurbinectedin. The FDA reviewed the application supported by pivotal Phase III data. Roche/Genentech, sponsor of Tecentriq, provided aligned communications on the approval but did not submit a separate supplemental BLA.

Clinical Data

The FDA approval was supported primarily by results from the Phase III IMforte trial (NCT05091567), a randomized, open-label, multicenter study evaluating lurbinectedin (Zepzelca®) plus atezolizumab (Tecentriq®) versus atezolizumab alone in adult patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease had not progressed after first-line induction therapy with atezolizumab, carboplatin, and etoposide.

Key Findings:

• Progression-Free Survival (PFS): Median PFS was 5.4 months in the combination arm versus 2.1 months in the atezolizumab monotherapy arm (HR = 0.54; p < 0.0001).
• Overall Survival (OS): Median OS was 13.2 months versus 10.6 months, respectively (HR = 0.73; p = 0.0174).
• Objective Response Rate (ORR): Significantly higher in the combination arm (exact ORR data if available can be inserted).
• Safety Profile: Treatment-related adverse events (TRAEs) occurred in 83.5% of patients in the combination arm versus 40.0% in the monotherapy arm. Grade 3/4 TRAEs were 25.6% vs. 5.8%; grade 5 TRAEs were rare (0.8% vs. 0.4%). Discontinuation due to adverse events occurred in 6.2% vs. 3.3% of patients, respectively.

These results demonstrate a clinically meaningful improvement in both PFS and OS, supporting the use of lurbinectedin plus atezolizumab as a first-line maintenance option for ES-SCLC.

Strategic Implications

For Jazz Pharmaceuticals, this represents a critical expansion of Zepzelca beyond its second-line monotherapy use into the much larger frontline ES-SCLC population. For Roche, the decision strengthens Tecentriq’s position as a backbone immunotherapy in SCLC, now partnered with an additional chemotherapy backbone beyond carboplatin/etoposide.

References

1. FDA. FDA approves lurbinectedin combination with atezolizumab for extensive-stage small cell lung cancer. October 3, 2025.
2. Jazz Pharmaceuticals. FDA Approves Zepzelca® (lurbinectedin) in Combination with Tecentriq® (atezolizumab) for the First-Line Treatment of Adults with Extensive-Stage Small Cell Lung Cancer. October 3, 2025.
3. Roche. FDA approval of Tecentriq® in combination with Zepzelca® for extensive-stage small cell lung cancer. October 3, 2025.