Shots:
- Jazz Pharmaceuticals and partners presented seven abstracts from their oncology development program at ASCO 2025
- Robert Iannone, EVP, Global Head of Research and Development, and Chief Medical Officer at Jazz Pharmaceuticals, in an engaging discussion with PharmaShots, shared insights from the P-III IMforte trial assessing Zepzelca plus atezolizumab in first-line maintenance treatment for Extensive Stage Small Cell Lung Cancer
- Zepzelca plus atezolizumab is currently being evaluated in the 2SMALL phase I/II study in patients with relapsed SCLC
Saurabh: What do you see as the main implications of these IMforte trial results for the current standard of care in first-line maintenance treatment for ES-SCLC?
Robert: IMforte is the first global Phase 3 trial to demonstrate statistically significant and clinically meaningful improvements in both progression-free survival (PFS) and overall survival (OS) with a 1L maintenance regimen in ES-SCLC.
Following induction therapy with carboplatin, etoposide and atezolizumab (Tecentriq), patients who did not have disease progression were randomized to receive Zepzelca plus atezolizumab or atezolizumab alone. From the point of randomization, the median PFS was 5.4 months for the Zepzelca plus atezolizumab combination versus 2.1 months for atezolizumab alone (stratified HR = 0.54, 95% CI: 0.43–0.67; p < 0.0001), and median OS was 13.2 months versus 10.6 months (stratified hazard ratio [HR] = 0.73; 95% CI: 0.57–0.95; p = 0.0174). The combination reduced the risk of disease progression or death by 46% and the risk of death by 27% compared to atezolizumab alone.
Zepzelca plus atezolizumab demonstrated meaningful clinical benefit across the study population, reinforcing its potential role as a first-line maintenance option in ES-SCLC. This combination could provide physicians with a practice-changing option in an aggressive cancer type with limited survival and few treatment options.
Saurabh: Given these findings, how do you think treatment options might change for patients who aren’t able to receive therapy at the time of disease progression?
Robert: The results from the IMforte trial build on the demonstrated efficacy of Zepzelca in second-line small cell lung cancer (SCLC) and now support its use earlier in the treatment journey as part of a combination therapy proactively in front line. The findings demonstrate the important progress that has been made in delaying progression and extending survival for patients with this aggressive disease who have limited options following induction therapy.
Saurabh: Could you walk us through the next steps in the regulatory approval process for this combination, and what kind of timeline should we expect for potential FDA approval?
Robert: We recently announced that the FDA accepted our supplemental New Drug Application (sNDA) for extensive-stage small cell lung cancer (ES-SCLC) for Priority Review, with a Prescription Drug User Fee Act (PDUFA) action date of October 7, 2025. We look forward to working with all relevant stakeholders to bring this first-line maintenance option to patients with ES-SCLC as quickly as possible, pending FDA review and approval.
Saurabh: How would you compare the safety outcomes observed in the IMforte trial to what we’ve seen previously with Zepzelca and atezolizumab, whether used alone or together?
Robert: Safety was consistent with the known safety profiles of Zepzelca and atezolizumab. Grade 3-4 TRAEs (treatment-related adverse events) occurred in 25.6% of patients in the Zepzelca plus atezolizumab arm vs. 5.8% in the atezolizumab arm. Grade 5 TRAEs were rare (0.8%), and treatment discontinuation due to AEs was low (6.2%), indicating the combination was manageable even in a maintenance setting.
Saurabh: From your perspective, what are the most important factors payers and healthcare systems should consider when evaluating this new combination as a standard first-line maintenance therapy?
Robert: This combination is the first maintenance treatment to have a positive Phase 3 readout in this disease setting. We believe that these results are practice-changing and will serve as a new standard of care for ES-SCLC first-line maintenance.
Saurabh: Looking ahead, how do you anticipate the adoption of Zepzelca plus atezolizumab as a first-line maintenance option will shape the treatment landscape for ES-SCLC over the next five years?
Robert: SCLC is the most aggressive form of lung cancer with an extremely poor prognosis and, despite treatment advances, a significant medical need remains.
The approval of atezolizumab plus chemotherapy (carboplatin and etoposide) for ES-SCLC was the first clinically meaningful improvement in the initial treatment of ES-SCLC in more than twenty years. It remains the first-line standard of care for these patients. However, despite the effectiveness of atezolizumab plus chemotherapy, most patients experience disease progression, and the prognosis remains poor with a two-year survival rate of ~20% (median OS: 12.3 months). There is a need for further investigation into whether targeting multiple pathways at the same time may further improve patients’ prognosis and deliver better long-term outcomes.
IMforte is the first global Phase 3 trial to demonstrate statistically significant and clinically meaningful improvements in both progression-free survival (PFS) and overall survival (OS) with a 1L maintenance regimen in ES-SCLC. This combination could provide physicians with a practice-changing option in an aggressive cancer type with limited survival and few treatment options.
Saurabh: Are there any plans to explore the use of Zepzelca and atezolizumab together in other cancer types, and what kind of impact could that have on clinical practice in the future?
Robert: The combination of Zepzelca plus atezolizumab showed promising efficacy in patients with relapsed SCLC in the 2SMALL phase I/II study [NCT04253145]. This was regardless of prior exposure to immunotherapy, including those with resistance to platinum. The associated safety profile was manageable.
At this time our focus is on securing FDA approval in first-line maintenance treatment of ES-SCLC and then commercial adoption of this combination treatment.
About the Author:
Robert Iannone
M.D., M.S.C.E. / CMO, EVP, Global Head of Research and Development
Robert Iannone has been Jazz’s executive vice president and global head of research and development since May 2019. Dr. Iannone oversees all aspects of preclinical research and clinical development, clinical operations and regulatory affairs. Dr. Iannone brings more than 18 years of experience in clinical drug development, having worked across therapeutic areas and phases of development, most recently on immuno-oncology programs at Merck, AstraZeneca and Immunomedics.
Related Post: Jazz Pharmaceuticals at ASCO 2025: Robert Iannone in a Stimulating Conversation with PharmaShots
