MHRA approves lurbinectedin plus atezolizumab for extensive-stage small cell lung cancer after first-line therapy, based on Phase III IMforte data.
Written By: Kalyani Boharapi,
M.Pharm (Reg. Affairs)
Reviewed By: Pharmacally Editorial Team
The UK Medicines and Healthcare products Regulatory Agency (MHRA) has approved lurbinectedin (Zepzelca) in combination with atezolizumab as maintenance treatment for adults with extensive-stage small cell lung cancer (ES-SCLC) whose disease has not progressed following first-line induction with atezolizumab, carboplatin, and etoposide. The September 23, 2026, marketing authorisation gives lurbinectedin a defined role in maintenance therapy after initial chemoimmunotherapy.
Phase III IMforte Trial Supported the Approval
The approval was supported by IMforte (GO43104), a Phase III, randomized, open-label, multicenter trial (NCT05091567). The study evaluated lurbinectedin plus atezolizumab against atezolizumab alone as maintenance therapy in patients with ES-SCLC following first-line induction with carboplatin, etoposide, and atezolizumab.
A total of 660 patients entered the induction phase, receiving four 21-day cycles of atezolizumab, carboplatin, and etoposide. Patients with an ongoing response or stable disease after induction could enter the maintenance phase. 483 patients were subsequently randomized, with 242 assigned to lurbinectedin plus atezolizumab and 241 to atezolizumab alone.
The trial had two primary efficacy endpoints: independent review facility-assessed progression-free survival (PFS) and overall survival (OS), both measured from randomization into the maintenance phase.
At the July 29, 2024, data cutoff, median OS was 13.2 months with lurbinectedin plus atezolizumab versus 10.6 months with atezolizumab alone. The stratified hazard ratio was 0.73 (95% CI, 0.57–0.95; P=0.0174).
Median PFS was 5.4 versus 2.1 months, respectively, with a stratified hazard ratio of 0.54 (95% CI, 0.43–0.67; P<0.0001).
Lurbinectedin Targets Tumour DNA
Lurbinectedin binds to DNA inside cancer cells, disrupting transcription and interfering with cancer-cell proliferation. It also suppresses the activity of certain tumour-associated immune cells that can contribute to tumour growth.
For the approved indication, lurbinectedin is administered by intravenous infusion over one hour once every 21 days. The treatment should be initiated and supervised by healthcare professionals in a hospital or clinical setting. In the IMforte trial, lurbinectedin was administered at 3.2 mg/m² intravenously on Day 1 of each 21-day maintenance cycle, alongside atezolizumab 1,200 mg.
Safety Profile Reflects Myelosuppressive Toxicities
The most common side effects reported with lurbinectedin include nausea, fatigue, anaemia, thrombocytopenia, and neutropenia. The Phase III study reported higher rates of myelosuppressive toxicities with the combination than with atezolizumab alone. Grade 3–4 adverse events occurred in 38% of patients receiving lurbinectedin plus atezolizumab compared with 22% in the atezolizumab group.
The MHRA will continue monitoring lurbinectedin through the UK Yellow Card pharmacovigilance system.
UK Authorisation Follows International Recognition Procedure
The MHRA granted the marketing authorisation to Pharma Mar, S.A. on September 23, 2026. The application was assessed through the International Recognition Procedure (IRP) Route B, with the European Medicines Agency serving as the reference regulator.
The approval establishes lurbinectedin plus atezolizumab as a maintenance treatment option for a specific ES-SCLC population following disease control with first-line atezolizumab, carboplatin, and etoposide. The regulatory decision is supported by the IMforte Phase III findings showing improvements in both PFS and OS, while continued pharmacovigilance will monitor the medicine’s safety in UK clinical practice.
Reference
MHRA approves lurbinectedin for adults with extensive-stage small cell lung cancer, MHRA, 23 September
A Phase III, Open-Label Study of Maintenance Lurbinectedin in Combination with Atezolizumab Compared with Atezolizumab in Participants with Extensive-Stage Small-Cell Lung Cancer (IMforte), ClinicalTrials.gov ID NCT05091567
About the Writer
Kalyani Boharapi (LinkedIn) is a pharmacy professional and healthcare writer currently pursuing an M.Pharm in Regulatory Affairs at Dr. D. Y. Patil College of Pharmacy, with interests in pharmaceutical regulations, drug development, and healthcare innovation. She has academic exposure to dossier preparation, scientific writing, and regulatory documentation. Kalyani has also completed certification courses in Generative AI, AI in Pharma, and Bioinformatics, and actively participates in pharmaceutical conferences to stay updated with emerging trends and advancements in the healthcare and pharmaceutical industry.