FDA Approves Tecentriq–Zepzelca Combo as FL Maintenance Therapy for ES-SC Lung Cancer

The U.S. Food and Drug Administration (FDA) has approved atezolizumab (Tecentriq) plus lurbinectedin (Zepzelca) as the first combination maintenance therapy for extensive-stage small cell lung cancer (ES-SCLC). In the Phase III IMforte trial, the regimen reduced disease progression or death by 46% and mortality by 27% versus Tecentriq alone, with median overall survival of 13.2 vs. 10.6 months and consistent safety.

This decision marks the first and only approved combination regimen for first-line maintenance in ES-SC Lung Cancer, addressing a critical gap in the management of a cancer type known for its high relapse rate and limited durable responses. The regimen is already recognized as a preferred option in the latest National Comprehensive Cancer Network® (NCCN) Clinical Practice Guidelines in Oncology, with a Category 2A recommendation.

A new standard for post-induction care in ES-SCLC

“The Tecentriq and Zepzelca combination provides a new option and a proactive approach in this setting shown to improve progression-free and overall survival in patients who haven't progressed after standard induction treatment with Tecentriq and chemotherapy. The approval may lead to a meaningful shift in how we manage this challenging disease and gives us a new tool to help to delay disease progression and extend survival,” said Dr. Roy Herbst, chief of medical oncology and hematology at Yale Cancer Center and Smilow Cancer Hospital.

The approval is based on findings from the Phase III IMforte trial (NCT05091567), a randomized, open-label study that evaluated the combination of atezolizumab plus lurbinectedin versus atezolizumab alone as maintenance therapy after standard induction.

IMforte: Improved survival outcomes

In IMforte, 660 patients received induction therapy with atezolizumab, carboplatin, and etoposide over four 21-day cycles. Patients whose disease had not progressed (n=483) were randomized 1:1 to receive either the Tecentriq–lurbinectedin combination or Tecentriq alone until progression or unacceptable toxicity.

The combination significantly improved both progression-free survival (PFS) and overall survival (OS) compared to Tecentriq monotherapy:

• Median OS: 13.2 months vs. 10.6 months, (HR 0.73; 95% CI 0.57–0.95; p = 0.0174)
• Median PFS: 5.4 months vs. 2.1 months, (HR 0.54; 95% CI 0.43–0.67; p < 0.0001)

These results correspond to a 46% reduction in the risk of disease progression or death and a 27% reduction in the risk of death, establishing the regimen as a new benchmark for maintenance therapy in ES-SCLC.

Dr. Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development at Genentech, emphasized the clinical impact: “The Tecentriq and lurbinectedin combination reduced the risk of disease progression or death by nearly half. We are proud to deliver this advancement for the small cell lung cancer community in partnership with Jazz Pharmaceuticals, as it reflects our abiding commitment to improving outcomes in the hardest-to-treat cancers.”

Safety profile and tolerability

Safety outcomes in IMforte were consistent with the known profiles of both agents. No new or unexpected safety signals were reported.

• Atezolizumab carries established warnings for severe or fatal immune-mediated reactions, infusion-related events, and embryo-fetal toxicity.
• Lurbinectedin is associated with myelosuppression, hepatotoxicity, extravasation risk, rhabdomyolysis, and embryo-fetal toxicity.

Expanding on Tecentriq’s foundation in SCLC

This new approval extends Tecentriq’s established role in ES-SCLC. In 2019, Tecentriq became the first new treatment in over two decades to demonstrate a survival benefit in this population when added to platinum–etoposide chemotherapy (IMpower133 trial). The addition of lurbinectedin in the maintenance setting now offers an opportunity to further delay relapse and extend survival.