PharmaMar and Jazz Pharmaceuticals have announced positive top-line results from the Phase 3 IMforte trial, evaluating Zepzelca® (lurbinectedin) in combination with the PD-L1 inhibitor atezolizumab (Tecentriq®) as a maintenance treatment for adults with extensive-stage Small Cell Lung Cancer (ES-SCLC). The study showed a statistically significant improvement in both overall survival (OS) and progression-free survival (PFS) compared to atezolizumab alone.
The IMforte trial (NCT05091567) is a randomized, multicenter study that enrolled patients with ES-SCLC who had previously undergone induction therapy with carboplatin, etoposide, and atezolizumab. Patients with an ongoing response or stable disease were then randomized to receive either lurbinectedin plus atezolizumab or atezolizumab alone as maintenance therapy. The primary endpoints were OS and PFS, assessed by an independent review facility (IRF).
Clinical Impact and Regulatory Plans
According to Luis Paz-Ares, M.D., Ph.D., head of medical oncology at the Hospital Universitario 12 de Octubre in Madrid, Spain, and IMforte trial principal investigator, "These trial results demonstrate the efficacy of lurbinectedin, in combination with standard-of-care atezolizumab for patients in first-line maintenance treatment, a much-needed advancement for patients with extensive disease."
Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals, stated, "We are pleased with these clinically meaningful results and plan to submit an sNDA in the first half of 2025 to support this combination in the first-line maintenance setting."
PharmaMar will also submit a marketing authorisation application (MAA) to the EMA in the first half of 2025 to request regulatory approval in the European Union (EU).
Safety and Tolerability
The combination of lurbinectedin and atezolizumab was generally well-tolerated. Preliminary safety data from the ongoing trial are consistent with the known safety profiles of both drugs, with no new safety signals observed in the combination arm.
Lurbinectedin in SCLC Treatment
Lurbinectedin monotherapy is currently a standard of care in second-line SCLC. Javier Jiménez, Chief Medical Officer of PharmaMar, noted that in Europe, lurbinectedin is approved in Switzerland, and early access and compassionate use programs have allowed some European patients to benefit from the drug.
About Lurbinectedin
Zepzelca® (lurbinectedin) is a selective inhibitor of oncogenic transcription programs. It inhibits oncogenic transcription in tumor-associated macrophages, downregulating the production of cytokines essential for tumor growth. Transcriptional addiction is a recognized target in diseases lacking other actionable targets.
