Jazz Pharmaceuticals Reports Landmark Phase 3 Results for Zepzelca and Tecentriq Combo as First-Line Maintenance Therapy in Extensive-Stage Small Cell Lung Cancer
Jazz Pharmaceuticals plc has announced highly promising results from its global Phase 3 IMforte clinical trial, which evaluated the efficacy of a novel first-line maintenance therapy for patients with extensive-stage small cell lung cancer (ES-SCLC). The combination of Zepzelca® (lurbinectedin) and atezolizumab (Tecentriq®) demonstrated statistically significant and clinically meaningful improvements in both progression-free survival (PFS) and overall survival (OS) compared to atezolizumab alone. These findings mark a significant step forward in the treatment of a notoriously aggressive cancer type with limited therapeutic options.
The positive data were unveiled in a high-profile oral presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting, currently taking place in Chicago. Simultaneously, the full results were published in the prestigious medical journal The Lancet, further underscoring the potential clinical impact of this regimen. Based on these compelling findings, Jazz Pharmaceuticals has submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA), seeking approval for the Zepzelca-atezolizumab combination as a new standard maintenance therapy for ES-SCLC.
A Disease with High Unmet Needs
Small cell lung cancer is among the most aggressive forms of lung cancer, accounting for about 13–15% of all lung cancer cases. By the time of diagnosis, most patients present with extensive-stage disease, characterized by rapid tumor progression and widespread metastases. Treatment options are limited, and the overall prognosis is grim. According to estimates, approximately 30,000 new cases of SCLC are diagnosed annually in the United States alone, and only about 20% of patients survive longer than two years following diagnosis.
In this challenging clinical landscape, the IMforte trial represents a groundbreaking step forward. Not only does it offer new hope to patients, but it also provides oncologists with evidence-based tools to intervene earlier in the treatment continuum.
IMforte Study Design and Outcomes
The IMforte trial was designed to evaluate whether the addition of Zepzelca, a selective oncogenic transcription inhibitor, to atezolizumab, a PD-L1 immune checkpoint inhibitor, could improve outcomes when administered as first-line maintenance therapy following standard induction treatment. Prior to entering the maintenance phase of the trial, all 483 enrolled patients received four cycles of induction therapy consisting of carboplatin, etoposide, and atezolizumab. Those whose disease had not progressed were randomized to receive either the combination of Zepzelca plus atezolizumab or atezolizumab monotherapy.
The results clearly favored the combination arm. Patients treated with Zepzelca plus atezolizumab achieved a median progression-free survival of 5.4 months from the time of randomization, compared to just 2.1 months for those receiving atezolizumab alone. This translated to a 46% reduction in the risk of disease progression or death (stratified HR = 0.54; 95% CI: 0.43–0.67; p < 0.0001).
Overall survival outcomes were similarly compelling. Patients in the combination group achieved a median OS of 13.2 months versus 10.6 months in the monotherapy group, representing a 27% reduction in the risk of death (stratified HR = 0.73; 95% CI: 0.57–0.95; p = 0.0174). These dual primary endpoint successes position the Zepzelca-atezolizumab combination as the first therapy in a Phase 3 setting to significantly improve both PFS and OS in the first-line maintenance treatment of ES-SCLC.
Safety and Tolerability
The safety profile of the Zepzelca and atezolizumab combination was generally consistent with known toxicities of each agent, and no new or unexpected adverse events were reported. Treatment-related adverse events (TRAEs) occurred in 83.5% of patients receiving the combination therapy, compared to 40.0% in the atezolizumab monotherapy group. Grade 3 or 4 TRAEs occurred in 25.6% of patients in the combination arm versus 5.8% in the monotherapy arm.
Serious adverse events, including Grade 5 TRAEs, were rare. Two patients in the combination group experienced fatal events (sepsis and febrile neutropenia), while one patient in the monotherapy group died due to sepsis. The rate of treatment discontinuation due to adverse events was relatively low in both groups—6.2% for the combination arm and 3.3% for the monotherapy arm—highlighting the manageable toxicity profile of the regimen.
Importantly, patients in the combination arm remained on treatment twice as long as those in the monotherapy group, with a median maintenance duration of 4.2 months versus 2.1 months. This longer duration of disease control reflects the clinical benefit of the Zepzelca and atezolizumab combination.
Expert Commentary
Leading oncologists involved in the trial emphasized the significance of these findings for patients with ES-SCLC. Dr. Luis Paz-Ares, M.D., Ph.D., Head of Medical Oncology at Hospital Universitario 12 de Octubre in Madrid and principal investigator of the IMforte study, noted the transformative potential of this treatment strategy.
“Small cell lung cancer is an aggressive and devastating disease,” said Dr. Paz-Ares. “At the time of diagnosis, the large majority of patients have already progressed to extensive-stage disease, and only one out of five survive longer than two years. The IMforte results are very encouraging, showing a potentially practice-changing option that could improve survival for patients with a very high unmet need.”
Dr. Stephen V. Liu, M.D., Associate Professor of Medicine at the Lombardi Comprehensive Cancer Center, Georgetown University, and a co-investigator on the trial, echoed those sentiments. “Unfortunately, a significant number of patients are not able to receive any therapy at the time of progression,” he said. “This combination gives oncologists a new evidence-based option to help patients before progression occurs and improve outcomes in a setting where options have been limited.”
Jazz Pharmaceuticals’ Commitment to Oncology Innovation
Rob Iannone, M.D., M.S.C.E., Executive Vice President, Global Head of Research and Development, and Chief Medical Officer at Jazz Pharmaceuticals, underscored the company’s long-term commitment to advancing treatment options in oncology.
“The IMforte trial results underscore the potential of Zepzelca with atezolizumab to deliver clinically meaningful benefit as a first-line maintenance option for patients with extensive-stage small cell lung cancer,” said Dr. Iannone. “This is a significant advance for these patients and represents important progress in expanding Zepzelca’s potential utility earlier in the treatment journey. We look forward to engaging with the FDA to bring this indication to market as quickly as possible.”
Next Steps and Investor Update
In light of the promising results from IMforte, Jazz Pharmaceuticals has filed a supplemental New Drug Application with the FDA and anticipates regulatory discussions in the coming months. The company also plans to host an investor webcast on June 10 at 4:30 p.m. ET / 9:30 p.m. IST to provide additional insights into the trial data. The webcast will feature commentary from a leading expert in small cell lung cancer and senior members of Jazz’s management team.
As the oncology community continues to grapple with the challenges of treating small cell lung cancer, the IMforte trial offers a rare beacon of hope. If approved, the Zepzelca-atezolizumab combination could redefine the standard of care for patients with extensive-stage disease—offering longer survival, better disease control, and a new frontier in maintenance therapy.
