Written By: Riya Bhilare BPharm and Divyanjali Godage BPharm
Reviewed By: Pharmacally Editorial Team
In October 2025, the U.S. Food and Drug Administration (FDA) granted approval for the combination of Zepzelca (lurbinectedin) from Jazz Pharmaceuticals and Tecentriq (Atezolizumab) from Roche as a maintenance treatment for adults with extensive-stage small cell lung cancer (ES-SCLC). This approval is for patients whose disease has not progressed after first-line induction therapy with Atezolizumab, carboplatin, and etoposide. It represents the first and only combination therapy approved for first-line maintenance in ES-SCLC, a highly aggressive cancer with limited treatment options and a high relapse rate after initial therapy.
Jazz Pharmaceuticals plc is the MAH and manufacturer of Zepzelca, while Roche (through its member company Genentech) is the MAH for Tecentriq and Tecentriq Hybreza (Atezolizumab and hyaluronidase-tqjs). Both companies collaborated on this approved maintenance treatment regimen for ES-SCLC.
About Drugs
Zepzelca (Lurbinectedin)
Zepzelca is an anticancer chemotherapy agent that acts by binding to the DNA minor groove, disrupting oncogenic transcription and triggering DNA strand breaks. This dual action results in impaired replication and apoptosis of cancer cells. In addition to its direct cytotoxic effect, lurbinectedin reduces the activity of tumor-associated macrophages in the tumor microenvironment, which are known to support cancer growth. The drug first received accelerated FDA approval in June 2020 for patients with metastatic small cell lung cancer (SCLC) who had progressed following platinum-based chemotherapy. That approval was based on its demonstrated activity in heavily pre-treated patients, an area with very limited options. The current FDA decision broadens its role by authorizing its use in combination with Tecentriq as maintenance therapy in extensive-stage SCLC, where it has now shown the ability to extend progression-free and overall survival.
Tecentriq (Atezolizumab)
Tecentriq is a monoclonal antibody that targets programmed death-ligand 1 (PD-L1), a protein tumors use to evade the immune system. By blocking the PD-L1 interaction with PD-1 and B7.1 receptors, Tecentriq restores the ability of T-cells to recognize and attack cancer cells. This mechanism of immune checkpoint inhibition has reshaped the treatment landscape across multiple cancers. In extensive-stage SCLC, Tecentriq was previously approved in combination with platinum–etoposide chemotherapy as first-line therapy, based on the IMpower133 study. That approval represented a significant milestone, as it was the first advance in frontline ES-SCLC treatment in over 20 years. The recent approval to use Tecentriq together with Zepzelca in the maintenance setting builds on its role in SCLC, showing that combining immune checkpoint inhibition with a transcription-inhibiting chemotherapy agent can provide additive survival benefit for patients facing this aggressive disease.
About Extensive-Stage Small Cell Lung Cancer
Extensive-stage small cell lung cancer (ES-SCLC) represents the most advanced form of small cell lung cancer, accounting for two-thirds of all newly diagnosed SCLC cases. It is characterized by rapid tumor proliferation and early spreading to organs such as the liver, brain, and bone, and high initial sensitivity to chemotherapy. Despite early responsiveness, relapse occurs quickly in the majority of patients, and survival outcomes remain poor. Historically, the standard of care involved platinum-based chemotherapy, which provided only modest improvements in overall survival.
The recent approval of Tecentriq in combination with Zepzelca as maintenance therapy directly reports this unmet need by offering a regimen that delays disease progression and also provides a measurable survival advantage.
Clinical Evidence for Approval
Study Design
The Phase III IMforte trial (NCT05091567) was a randomized, open-label, global study evaluating the role of maintenance therapy in patients with extensive-stage small cell lung cancer (ES-SCLC). Eligible patients were those who had not experienced disease progression following induction treatment with Tecentriq (Atezolizumab), carboplatin, and etoposide. After induction, patients were randomized in a 1:1 ratio to receive Tecentriq plus Zepzelca (lurbinectedin) or Tecentriq alone as maintenance therapy. The study’s primary endpoint was progression-free survival (PFS), with overall survival (OS) as a key secondary endpoint. Other outcomes included safety, tolerability, and exploratory measures such as duration of response and quality of life.
Results
the study showed significant benefits with the addition of Zepzelca to Tecentriq maintenance therapy. Patients in the combination arm had a 46% reduction in the risk of disease progression or death compared to those on Tecentriq alone. Median PFS was 5.4 months with the combination versus 2.1 months with Tecentriq alone. For overall survival, the combination reduced the risk of death by 27%, Median OS was 13.2 months in the combination group compared with 10.6 months in the Tecentriq-alone group. These findings establish the combination as a more effective maintenance option, extending both disease control and overall survival in ES-SCLC.
These results demonstrate significant improvement in progression-free and overall survival with the combination maintenance therapy.
Safety Profile
The safety profile of the combination drugs was generally consistent with known effects of each drug, with no new safety signals detected. Important adverse effects include myelosuppression with Zepzelca severe neutropenia, thrombocytopenia, anemia, febrile neutropenia, and sepsis. Monitoring blood counts and administering granulocyte colony-stimulating factor (G-CSF) as appropriate are recommended to manage neutropenia risks during combination therapy.
Public Health Implications
This FDA approval marks a significant advancement in treatment options for ES-SCLC, a disease with historically limited maintenance therapies and poor patient outcomes. Introducing an effective combination maintenance therapy offers clinicians a new tool to extend progression-free and overall survival, thus potentially improving quality of life and lifespan for many patients. The regimen has also been incorporated into the U.S. National Comprehensive Cancer Network (NCCN) Guidelines as a preferred maintenance option for ES-SCLC after induction therapy.
Key Opinions
Dr. Roy Herbst (Yale Cancer Center) described this approval as a hopeful advance for patients and families in the high-risk post-induction period, noting that the Tecentriq + Zepzelca combination offers a more proactive approach shown to delay progression and extend survival in those who have not progressed after standard induction therapy. Dr. Rob Iannone (CMO, Jazz Pharmaceuticals) highlighted the clinical value of delaying disease progression in this aggressive cancer type, commenting that “extending the time to progression, and ultimately survival, will be clinically valuable” in a disease with rapid relapse. Meanwhile, Dr. Levi Garraway (Roche CMO) emphasized pride in bringing this advancement to the SCLC community, and underscored the collaborative effort with Jazz to improve outcomes in one of oncology’s hardest-to-treat cancers.
References
FDA approves Roche’s Tecentriq plus lurbinectedin as first-line maintenance therapy for extensive-stage small cell lung cancer, Roche, 03 Oct 2025, https://www.roche.com/investors/updates/inv-update-2025-10-03
FDA Approves Zepzelca® (lurbinectedin) and Atezolizumab (Tecentriq®) Combination as First-Line Maintenance Therapy for Extensive-Stage Small Cell Lung Cancer, Jazz Pharmaceutics, 02 Oct 2025, https://investor.jazzpharma.com/news-releases/news-release-details/fda-approves-zepzelcar-lurbinectedin-and-atezolizumab-tecentriqr
FDA Approves Genentech’s Tecentriq Plus Lurbinectedin as First-Line Maintenance Therapy for Extensive-Stage Small Cell Lung Cancer, Genentech, 02 Oct 2025, https://www.gene.com/media/press-releases/15079/2025-10-02/fda-approves-genentechs-tecentriq-plus-l