FDA Approves Zepzelca Plus Tecentriq for Extensive-Stage Small Cell Lung Cancer

The U.S. Food and Drug Administration (FDA) has approved Zepzelca (lurbinectedin) in combination with Tecentriq (atezolizumab) or Tecentriq Hybreza (atezolizumab and hyaluronidase-tqjs) for the treatment of adults with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed after first-line induction therapy with Tecentriq or Tecentriq Hybreza, carboplatin and etoposide. The approval was announced in a news release issued by the regulatory agency.

The treatment’s effectiveness was determined in the IMforte randomized, multicenter, open-label trial of patients receiving first-line treatment for ES-SCLC, which is lung cancer that has spread beyond the lungs to other parts of the body. The trial included 483 patients with ES-SCLC whose disease had not progressed after four cycles of Tecentriq, carboplatin and etoposide and were evenly randomized to receive either Zepzelca in combination with Tecentriq administered intravenously (via IV) or Tecentriq IV alone until disease progression or unacceptable toxicity, the agency explained.

The median overall survival was 13.2 months in the Zepzelca with Tecentriq arm and 10.6 months in the Tecentriq arm, while the median progression-free survival times were 5.4 months and 2.1 months, respectively, the FDA reported.

Zepzelca, as defined by the National Cancer Institute on its website, is a type of alkylating agent that may kill cancer cells by damaging their DNA and stopping them from dividing.

The FDA noted that the prescribing information for Zepzelca includes warnings and precautions for myelosuppression, hepatotoxicity, extravasation resulting in tissue necrosis, rhabdomyolysis and embryo-fetal toxicity, while the prescribing information for Tecentriq and Tecentriq Hybreza includes warnings and precautions for severe and fatal immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic HSCT and embryo-fetal toxicity.

The agency stated that the recommended dosage of Zepzelca is 3.2 mg/m² administered by IV infusion every 21 days until disease progression or unacceptable toxicity. The recommended Tecentriq dose is 840 mg every two weeks, 1200 mg every three weeks or 1680 mg every four weeks by intravenous infusion until disease progression or unacceptable toxicity. The recommended dosage of Tecentriq Hybreza is 1875 mg of Tecentriq and 30,000 units of hyaluronidase administered subcutaneously every three weeks until disease progression or unacceptable toxicity.

Expert Insight on the IMforte Clinical Trial

Dr. Prantesh Jain, a medical oncologist at Roswell Park Comprehensive Cancer Center, in Buffalo, New York, where he also serves as an assistant professor of Oncology in the Department of Medicine who also works at the State University of New York at Buffalo as a clinical assistant professor, sat down with CURE’s editor-in-chief, Dr. Joshua K. Sabari, at the 2025 ASCO Annual Meeting, and discussed the significance of the IMforte clinical trial and its findings.

“SCLC continues to pose a significant challenge due to its rapid progression and the limited availability of effective second-line therapies. Notably, nearly 60% of these patients never reach second-line treatment because of rapid clinical deterioration,” he said. “The phase 3 IMforte trial enrolled 483 patients with extensive-stage SCLC to investigate whether the addition of Zepzelca to Tecentriq in the first-line maintenance setting provides a survival benefit compared to Tecentriq alone.”

“Patients who achieved stable disease, partial response, or complete response after induction chemo-immunotherapy with carboplatin, etoposide and Tecentriq were included. Patients with central nervous system metastasis were excluded. Approximately 3.2 months after induction, patients were randomized to receive maintenance therapy with either Zepzelca plus Tecentriq or Tecentriq alone. The primary endpoints were progression-free survival and overall survival, measured from the maintenance randomization,” Jain continued.

Jain concluded the conversation by saying that key findings demonstrated a markedly longer median progression-free survival in the combination therapy arm, reaching 5.4 months compared with 2.1 months in the Tecentriq-alone arm, reflecting both clinical and statistical significance. Median overall survival also improved, increasing from 10.6 months to 13.2 months. Additionally, the 12-month overall survival rate rose from 44% to 56% among patients receiving the combination regimen.

The confirmed objective response rate following induction chemo-immunotherapy nearly doubled, rising from 10.4% with Tecentriq alone to 19.4% in the combination arm. Toxicities were consistent with the expected profile of Zepzelca plus immunotherapy, primarily hematologic, and were more common in the combination group but generally manageable with supportive care.

Clinically, this study represents a practice-changing advance. It is the first phase 3 trial to show a definitive survival benefit in the first-line maintenance setting for ES-SCLC, Jain emphasized.

References

“FDA approves lurbinectedin in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs for extensive-stage small cell lung cancer,” by the U.S. FDA. U.S. FDA; Oct. 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-lurbinectedin-combination-atezolizumab-or-atezolizumab-and-hyaluronidase-tqjs-extensive?utm_medium=email&utm_source=govdelivery

“Zepzelca,” by the National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/zepzelca

“Recent SCLC Data May Impact How Patients Are Treated Day-to-Day,” by Ryan Scott. CURE; June 18, 2025. https://www.curetoday.com/view/recent-sclc-data-may-impact-how-patients-are-treated-day-to-day

Transcript has been edited for clarity and conciseness.

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