The U.S. Food and Drug Administration (FDA) has approved lurbinectedin (Zepzelca) in combination with atezolizumab (Tecentriq), or with atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza), as a maintenance treatment for adults with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed after initial therapy.
Efficacy was assessed in the IMforte trial (NCT05091567), a randomized, multicenter, open-label study involving 483 patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease had not progressed after initial treatment with atezolizumab, carboplatin, and etoposide. Participants were randomly assigned to receive either lurbinectedin plus atezolizumab or atezolizumab alone until disease progression or unacceptable toxicity.
Results showed a median overall survival of 13.2 months for the combination group versus 10.6 months for the atezolizumab-only group. Median progression-free survival was 5.4 months compared to 2.1 months, demonstrating a clear benefit for the combination therapy.
Lurbinectedin’s safety profile includes risks of myelosuppression, liver toxicity, tissue injury from infusion (extravasation), muscle breakdown (rhabdomyolysis), and fetal harm. Atezolizumab and its hyaluronidase formulation carry warnings for immune-related adverse reactions, infusion-related effects, post-transplant complications, and embryo-fetal toxicity.
The recommended dose of lurbinectedin is 3.2 mg/m² administered by intravenous infusion every 21 days until disease progression or unacceptable toxicity. Atezolizumab may be given intravenously at 840 mg every two weeks, 1,200 mg every three weeks, or 1,680 mg every four weeks under the same conditions. For the subcutaneous combination, atezolizumab and hyaluronidase-tqjs are administered as 1,875 mg of atezolizumab with 30,000 units of hyaluronidase every three weeks until progression or unacceptable toxicity.
This approval was reviewed under the FDA’s Project Orbis initiative, which enables concurrent evaluation of oncology drugs by multiple international regulatory agencies. The FDA collaborated with authorities in Australia, Canada, Israel, and Switzerland during this process. The review also utilized the Assessment Aid, a voluntary tool designed to streamline the FDA’s evaluation. The application received priority review status, and both lurbinectedin and atezolizumab were granted orphan drug designation, recognizing their role in addressing a rare and serious cancer type.
Learn more: FDA approves lurbinectedin in combination with atezolizumab
