FDA Approves Zepzelca® (lurbinectedin) and Atezolizumab (Tecentriq®) Combination as First-Line Maintenance Therapy for Extensive-Stage Small Cell Lung Cancer
Jazz Pharmaceuticals (Nasdaq: JAZZ) announced FDA approval on Oct 2, 2025 of Zepzelca (lurbinectedin) plus atezolizumab (or atezolizumab/hyaluronidase-tqjs) as the first-line maintenance therapy for adults with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed after induction with atezolizumab, carboplatin and etoposide.
The approval is based on Phase 3 IMforte results showing a 46% reduction in risk of progression or death and a 27% reduction in risk of death; median OS 13.2 vs 10.6 months (HR=0.73; p=0.0174) and median PFS 5.4 vs 2.1 months (HR=0.54; p<0.0001). The regimen was added to NCCN SCLC guidelines as a preferred maintenance option. Common adverse reactions (≥30%) include cytopenias, nausea, and fatigue.
Jazz Pharmaceuticals (Nasdaq: JAZZ) ha annunciato l'approvazione FDA il 2 ottobre 2025 di Zepzelca (lurbinectedin) insieme a atezolizumab (o atezolizumab/hyaluronidase-tqjs) come terapia di mantenimento di prima linea per adulti con carcinoma polmonare a piccole cellule esteso (ES-SCLC) la cui malattia non è progredita dopo l'induzione con atezolizumab, carboplatino ed etoposide.
L'approvazione si basa sui risultati della fase 3 IMforte che mostrano una riduzione del rischio di progressione o morte del 46% e una riduzione del rischio di morte del 27%; mediana di OS 13,2 mesi contro 10,6 mesi (HR=0,73; p=0,0174) e mediana di PFS 5,4 mesi contro 2,1 mesi (HR=0,54; p<0,0001). Il regime è stato inserito nelle linee guida NCCN SCLC come opzione di manutenzione preferita. Le reazioni avverse comuni (≥30%) includono citopenie, nausea e affaticamento.
Jazz Pharmaceuticals (Nasdaq: JAZZ) anunció la aprobación de la FDA el 2 de octubre de 2025 de Zepzelca (lurbinectedin) junto a atezolizumab (o atezolizumab/hialuronidasa-tqjs) como terapia de mantenimiento de primera línea para adultos con cáncer de pulmón de células pequeñas avanzado (ES-SCLC) cuyo mal estado no ha progresado tras la inducción con atezolizumab, carboplatino y etopósido.
La aprobación se basa en los resultados de la fase 3 IMforte, que muestran una reducción del riesgo de progresión o muerte del 46% y una reducción del riesgo de muerte del 27%; mediana de OS 13,2 meses Frente a 10,6 meses (HR=0,73; p=0,0174) y mediana de PFS 5,4 meses frente a 2,1 meses (HR=0,54; p<0,0001). El régimen se añadió a las guías NCCN SCLC como opción de mantenimiento preferida. Las reacciones adversas comunes (≥30%) incluyen citopenias, náuseas y fatiga.
Jazz Pharmaceuticals (나스닥: JAZZ)는 2025년 10월 2일에 Zepzelca (lurbinectedin)과 atezolizumab (또는 atezolizumab/hyaluronidase-tqjs)을 초기 유지 치료로 성인 ES-SCLC(확장형 소세포폐암)에서 항암화학요법으로 atezolizumab, carboplatin 및 etoposide의 유도 치료 후 병의 진행이 없었던 경우에 허가받았다고 발표했다.
승인은 Phase 3 IMforte 결과를 바탕으로 질병의 진행 또는 사망 위험이 46% 감소하고 사망 위험이 27% 감소했으며, 중앙 생존기간(OS) 13.2개월 대 10.6개월(HR=0.73; p=0.0174) 및 중앙 PFS 5.4개월 대 2.1개월(HR=0.54; p<0.0001)으로 나타났다. 이 치료법은 NCCN SCLC 가이드라인에 선호되는 유지 옵션으로 추가되었다. 일반적이고(≥30%)인 부작용으로는 혈액억제, 구역질(구토) 및 피로가 있다.
Jazz Pharmaceuticals (NASDAQ : JAZZ) a annoncé l'approbation de la FDA le 2 octobre 2025 de Zepzelca (lurbinectedin) associée à atezolizumab (ou atezolizumab/hyaluronidase-tqjs) comme thérapie d'entretien de première ligne pour les adultes atteints d'un cancer du poumon à petites cellules à un stade avancé (ES-SCLC) dont la maladie n'a pas progressé après une induction avec atezolizumab, carboplatine et étoposide.
L'approbation est basée sur les résultats de la phase 3 IMforte montrant une réduction du risque de progression ou de décès de 46% et une réduction du risque de décès de 27% ; médiane de l'OS à 13,2 mois contre 10,6 mois (HR=0,73; p=0,0174) et médiane du PFS à 5,4 mois contre 2,1 mois (HR=0,54; p<0,0001). Le régime a été intégré dans les directives NCCN SCLC comme option d'entretien privilégiée. Les réactions indésirables courantes (≥30%) incluent les cytopénies, les nausées et la fatigue.
Jazz Pharmaceuticals (Nasdaq: JAZZ) kündigte die Zulassung der FDA am 2. Oktober 2025 für Zepzelca (lurbinectedin) zusammen mit atezolizumab (oder atezolizumab/hyaluronidase-tqjs) als Erstlinien-Maintenance-Therapie für erwachsene Patienten mit ausgedehntem Kleinzell-Lungenkrebs (ES-SCLC) an, deren Erkrankung nach Induktion mit Atezo, Carboplatin und Etoposid nicht fortschreitet hat.
Die Zulassung basiert auf Phase-3-IMforte-Ergebnissen, die eine Reduktion des Risikos für Fortschreiten oder Tod um 46% sowie eine Reduktion des Risikos für Tod um 27% zeigen; Medianes OS 13,2 Monate vs 10,6 Monate (HR=0,73; p=0,0174) und Medianes PFS 5,4 Monate vs 2,1 Monate (HR=0,54; p<0,0001). Die Behandlung wurde in die NCCN-SCLC-Leitlinien als bevorzugte Mantenance-Option aufgenommen. Häufige unerwünschte Ereignisse (≥30%) sind Cytopenien, Übelkeit und Müdigkeit.
شركة Jazz Pharmaceuticals (ش.م.ع: JAZZ) أعلنت عن موافقة إدارة الغذاء والدواء الأمريكية في 2 أكتوبر 2025 على Zepzelca (lurbinectedin) مع atezolizumab (أو atezolizumab/hyaluronidase-tqjs) كعلاج صيانة من الخط الأول للبالغين المصابين بسرطان الرئة صغير الخلايا واسع الانتشار (ES-SCLC) الذي لم يتقدم مرضه بعد inductions مع atezolizumab و carboplatin و etoposide.
تعتمد الموافقة على نتائج التجربة من المرحلة 3 IMforte التي أظهرت انخفاضاً في مخاطر التقدم أو الوفاة بنسبة 46% وانخفاض مخاطر الوفاة بنسبة 27%؛ الوسيط للبقاء على قيد الحياة OS هو 13.2 شهراً مقابل 10.6 أشهر (HR=0.73؛ p=0.0174) والوسيط لـ PFS هو 5.4 أشهر مقابل 2.1 شهر (HR=0.54؛ p<0.0001). أضيف النظام إلى إرشادات NCCN SCLC كخيار صيانة مفضل. الآثار الضارة الشائعة (≥30%) تشمل قَصور الدم، والغثيان، والتعب.
Jazz Pharmaceuticals (纳斯达克: JAZZ) 于 2025年10月2日 获得 FDA 批准，将 Zepzelca (lurbinectedin) 与 atezolizumab（或 atezolizumab/hyaluronidase-tqjs）联合作为一线维持治疗，适用于在以 atezolizumab、卡铂和依托泊苷诱导治疗后疾病未进展的成人广泛期小细胞肺癌（ES-SCLC）。
该批准基于 III 期 IMforte 试验结果，显示进展或死亡风险降低 46%，死亡风险降低 27%；中位OS 为 13.2 个月对 10.6 个月（HR=0.73；p=0.0174），中位 PFS 为 5.4 个月对 2.1 个月（HR=0.54；p<0.0001）。该方案已被纳入 NCCN SCLC 指南，成为首选的维持治疗选项。常见不良反应（≥30%）包括血细胞减少、恶心和乏力。
- Phase 3 IMforte: PFS benefit HR=0.54 (median 5.4 vs 2.1 months)
- Phase 3 IMforte: OS benefit HR=0.73 (median 13.2 vs 10.6 months)
- FDA approval for first-line maintenance ES-SCLC on Oct 2, 2025
- NCCN added Zepzelca+atezolizumab as a preferred maintenance regimen
- Common adverse events ≥30%: decreased lymphocytes, platelets, hemoglobin, leukocytes, neutrophils
- Other frequent toxicities ≥30%: nausea and fatigue/asthenia
Insights
FDA approves the first first-line maintenance combination for ES-SCLC, showing clear PFS and OS benefits in Phase 3 IMforte.
This approval of Zepzelca (lurbinectedin) plus atezolizumab provides a new maintenance option after platinum/atezolizumab induction, supported by the Phase 3 IMforte trial results reported on Oct 2, 2025.
Why it matters: the trial showed a 46% reduction in risk of progression (PFS HR=0.54; p<0.0001) and a 27% reduction in risk of death (OS HR=0.73; p=0.0174), with median OS 13.2 vs 10.6 months and median PFS 5.4 vs 2.1 months versus atezolizumab alone, and the regimen was added to the NCCN Guidelines.
Monitor these concrete metrics from the randomized IMforte dataset: median OS (13.2 vs 10.6 months) and median PFS (5.4 vs 2.1 months).
Combination reduced the risk of disease progression or death by
Zepzelca and atezolizumab combination added to National Comprehensive Cancer Network® Guidelines for SCLC
For
The National Comprehensive Cancer Network® (NCCN®) updated the NCCN Clinical Practice Guidelines in Oncology® (NCCN Guidelines®) for SCLC to include the Zepzelca and atezolizumab combination as a preferred regimen for patients whose disease has not progressed following four cycles of platinum-based chemotherapy and atezolizumab induction.
"For people with extensive-stage small cell lung cancer and their families, the period after induction therapy is often filled with uncertainty, given the high risk of relapse," said Roy Herbst, M.D., Ph.D., deputy director and chief of medical oncology and hematology at Yale Cancer Center and Smilow Cancer Hospital. "The Zepzelca and Tecentriq combination provides a new option and a proactive approach in this setting shown to improve progression-free and overall survival in patients who haven't progressed after standard induction chemotherapy with Tecentriq and chemotherapy. The approval may lead to a meaningful shift in how we manage this challenging disease and gives us a new tool to help to delay disease progression and extend survival."
"ES-SCLC patients have good initial responses but then quickly progress. Extending the time to progression, and ultimately survival, will be clinically valuable, in particular in this fast-moving cancer," said Rob Iannone, M.D., M.S.C.E., executive vice president, global head of research and development, and chief medical officer of Jazz Pharmaceuticals. "The introduction of a new maintenance approach offers a new way to manage this aggressive disease and gives patients and their physicians a new treatment option with the potential to increase both PFS and OS. We're proud to advance the standard of care for ES-SCLC and we continue to pursue opportunities in cancer research that improve lives."
The FDA approval is based on results from the Phase 3 IMforte trial (NCT05091567), which showed that the Zepzelca and atezolizumab combination reduced the risk of disease progression or death by
The most common adverse reactions for Zepzelca in combination with atezolizumab including laboratory abnormalities, (≥
About Small Cell Lung Cancer
In the U.S., approximately 13 percent of lung cancers are small cell.2 Approximately 30,000 new cases of small cell lung cancer (SCLC) are reported in the U.S. each year.2,3 The risk for developing SCLC is much higher among current or former tobacco smokers; however, SCLC can also be caused by exposure to secondhand smoke, asbestos, some inhaled chemicals, radiation and air pollution. People with a family history of lung cancer may also be at a higher risk, too.4 SCLC is the most aggressive form of lung cancer and it tends to spread quickly to other parts of the body including the brain, liver and bone.5,6 A large percentage of SCLC patients on treatment briefly achieve a response, although the cancer often returns and is usually more aggressive and resistant to regimens that were previously effective.5
About Zepzelca® (lurbinectedin)
Zepzelca is an alkylating drug that binds guanine residues within DNA. This triggers a cascade of events that can affect the activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in disruption of the cell cycle and potentially cell death.1
In October 2025, the FDA approved Zepzelca in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, as maintenance treatment for adults with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed after first-line induction therapy with atezolizumab or atezolizumab and hyaluronidase-tqjs, carboplatin and etoposide.
In June 2020, the FDA approved Zepzelca under accelerated approval for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. This indication is approved under accelerated approval based on ORR and DOR. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
IMPORTANT SAFETY INFORMATION
Myelosuppression
ZEPZELCA can cause severe and fatal myelosuppression including febrile neutropenia and sepsis, thrombocytopenia and anemia.
Administer ZEPZELCA only to patients with baseline neutrophil count of at least 1,500 cells/mm3 and platelet count of at least 100,000/mm3. To reduce the risk of febrile neutropenia during treatment with ZEPZELCA in combination with atezolizumab or atezolizumab and hyaluronidase-tqjs, administer granulocyte colony-stimulating factor (G-CSF). Monitor blood counts including neutrophils, red blood cells and platelets prior to each ZEPZELCA administration. For neutrophil count less than 500 cells/mm3 or any value less than lower limit of normal, administer G-CSF. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity.
In the IMforte study, primary prophylaxis of G-CSF was administered to
Based on laboratory values, decreased platelets occurred in
Based on laboratory values, decreased hemoglobin occurred in
Hepatotoxicity
ZEPZELCA can cause hepatotoxicity which may be severe.
Monitor liver function tests prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. Withhold, reduce the dose, or permanently discontinue ZEPZELCA based on severity.
In the IMforte study, based on laboratory values, increased alanine aminotransferase (ALT) occurred in
Extravasation Resulting in Tissue Necrosis
Extravasation of ZEPZELCA can cause skin and soft tissue injury, including necrosis requiring debridement. Consider use of a central venous catheter to reduce the risk of extravasation, particularly in patients with limited venous access. Monitor patients for signs and symptoms of extravasation during the ZEPZELCA infusion. If extravasation occurs, immediately discontinue the infusion, remove the infusion catheter, and monitor for signs and symptoms of tissue necrosis. The time to onset of necrosis after extravasation may vary.
In the IMforte study, extravasation resulting in skin necrosis occurred in one patient who received ZEPZELCA in combination with atezolizumab.
Administer supportive care and consult with an appropriate medical specialist as needed for signs and symptoms of extravasation. Administer subsequent infusions at a site that was not affected by extravasation.
Rhabdomyolysis
Rhabdomyolysis has been reported in patients treated with ZEPZELCA.
Monitor creatine phosphokinase (CPK) prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. Withhold or reduce the dose based on severity.
In the IMforte study, among 235 patients who had a creatine phosphokinase laboratory evaluation, increased creatine phosphokinase occurred in
Embryo-Fetal Toxicity
ZEPZELCA can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise female patients of reproductive potential to use effective contraception during treatment with ZEPZELCA and for 6 months after the last dose. Advise male patients with female partners of reproductive potential to use effective contraception during treatment with ZEPZELCA and for 4 months after the last dose.
Lactation
There are no data on the presence of ZEPZELCA in human milk, however, because of the potential for serious adverse reactions from ZEPZELCA in breastfed children, advise women not to breastfeed during treatment with ZEPZELCA and for 2 weeks after the last dose.
ADVERSE REACTIONS
Serious adverse reactions occurred in
The most common adverse reactions (≥
DRUG INTERACTIONS
Effect of CYP3A Inhibitors and Inducers
Avoid coadministration with a strong or a moderate CYP3A inhibitor (including grapefruit and
Avoid coadministration with a strong CYP3A inducer as it may decrease systemic exposure to lurbinectedin, which may decrease the efficacy of ZEPZELCA.
GERIATRIC USE
Of the 242 patients with ES-SCLC treated with ZEPZELCA and atezolizumab in IMforte, 124 (
HEPATIC IMPAIRMENT
Avoid administration of ZEPZELCA in patients with severe hepatic impairment. If administration cannot be avoided, reduce the dose. Monitor for increased adverse reactions in patients with severe hepatic impairment.
Reduce the dose of ZEPZELCA in patients with moderate hepatic impairment. Monitor for increased adverse reactions in patients with moderate hepatic impairment.
No dose adjustment of ZEPZELCA is recommended for patients with mild hepatic impairment.
Please see accompanying full Prescribing Information. https://pp.jazzpharma.com/pi/zepzelca.en.USPI.pdf
ZEPZELCA is a trademark of Pharma Mar, S.A. used by Jazz Pharmaceuticals under license.
Tecentriq (atezolizumab) and Tecentriq Hybreza (atezolizumab and hyaluronidase-tqjs) are registered trademarks of Genentech, a member of the Roche Group.
About Jazz Pharmaceuticals
Jazz Pharmaceuticals plc (Nasdaq: JAZZ) is a global biopharma company whose purpose is to innovate to transform the lives of patients and their families. We are dedicated to developing potentially life-changing medicines for people with serious diseases – often with limited or no therapeutic options. We have a diverse portfolio of marketed medicines, including leading therapies for sleep disorders and epilepsy, and a growing portfolio of cancer treatments. Our patient-focused and science-driven approach powers pioneering research and development advancements across our robust pipeline of innovative therapeutics in oncology and neuroscience. Jazz is headquartered in Dublin, Ireland with research and development laboratories, manufacturing facilities and employees in multiple countries committed to serving patients worldwide. Please visit www.jazzpharmaceuticals.com for more information.
Contacts:
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Kristin Bhavnani
Head of Global Corporate Communications
Jazz Pharmaceuticals plc
CorporateAffairsMediaInfo@jazzpharma.com
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Jazz Investor Contact:
Jack Spinks
Executive Director, Investor Relations
Jazz Pharmaceuticals plc
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1ZEPZELCA (lurbinectedin) Prescribing Information. |
2Alvarado-Lunda G, Morales-Espinosa D. Treatment for small cell lung cancer, where are we now? – A review. Transl Lung Cancer Res. 2016;5(1):26-38. |
3SEER Explorer Lung and Bronchus Cancer, Recent Trends in SEER Incidence Rates, 2000-2016, by Age, https://seer.cancer.gov/explorer Updated June 27, 2024. Accessed October 1, 2025. |
4American Cancer Society. Small cell lung cancer causes, risk factors, and prevention. https://www.cancer.org/content/dam/CRC/PDF/Public/8709.00.pdf. Updated May 16, 2016. Accessed September 22, 2025. |
5American Cancer Society. What is lung cancer? https://www.cancer.org/cancer/lung-cancer/about/what-is.html. Updated January 29, 2024. Accessed October 1, 2025. |
6American Cancer Society. Small cell lung cancer stages. https://www.cancer.org/cancer/lung-cancer/detection-diagnosis-staging/staging-sclc.html. Updated January 29, 2024. Accessed October 1, 2025. |
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FAQ
What did Jazz Pharmaceuticals announce on Oct 2, 2025 about JAZZ and ES-SCLC?
How much did the Zepzelca and atezolizumab combination improve survival in the IMforte trial (JAZZ)?
What progression-free survival benefit did the IMforte trial report for JAZZ's combo?
Did clinical guidelines change after the JAZZ approval for Zepzelca (JAZZ)?
What are the most common adverse reactions for Zepzelca plus atezolizumab noted in the press release?
