Specialised Therapeutics has received regulatory approval in Australia and Singapore for Zepzelca (lurbinectedin) in combination with Tecentriq (atezolizumab) as a first-line maintenance treatment for adults with extensive-stage small cell lung cancer (ES-SCLC). The approvals, obtained through the US FDA’s Project Orbis framework, mark the eighth time the Singapore-headquartered company has navigated that collaborative review process since 2021. Lurbinectedin, developed by Spanish biopharmaceutical company PharmaMar and derived from a marine compound, is an alkylating agent that acts as a selective inhibitor of oncogenic transcription programs. The European Medicines Agency’s Committee for Medicinal Products for Human Use has also issued a positive opinion recommending approval of lurbinectedin in Europe, the company said.
The approved indication covers maintenance treatment for ES-SCLC in adult patients whose disease has not progressed following first-line induction therapy with atezolizumab, carboplatin, and etoposide. The decisions were made based on data from the IMforte trial, a randomized, multicenter, open-label Phase III study enrolling 660 treatment-naive patients with ES-SCLC across 96 hospitals in 13 countries. Of those, 483 patients who responded to induction therapy were randomized to receive either lurbinectedin plus atezolizumab (LU-AT, n=242) or atezolizumab monotherapy (AT, n=241) as maintenance. The trial, published in The Lancet in June 2025, reported median progression-free survival of 5.4 months in the LU-AT arm versus 2.1 months with atezolizumab alone, and median overall survival of 13.2 months versus 10.6 months. Treatment-related adverse events occurred in 83.5% of patients receiving LU-AT compared with 40% in the atezolizumab monotherapy arm. Grade 3 or 4 adverse events were recorded in 25.6% of the LU-AT group versus 5.8% in the AT group, and treatment discontinuation due to adverse events occurred in 6.2% and 3.3% of patients, respectively. The most common adverse reactions in the combination arm, occurring in 30% or more of patients, included decreased lymphocytes, platelets, hemoglobin, leukocytes, and neutrophils, as well as nausea and fatigue. The company said no new or unexpected safety signals were identified.
SCLC accounts for approximately 10%–15% of all lung cancer diagnoses and carries a five-year survival rate of under 7%, according to data cited in the press release. The disease frequently presents at an advanced stage, limiting surgical options and contributing to high relapse rates. In Australia, lung cancer is the leading cause of cancer death, with an estimated 15,000 diagnoses and 9,000 deaths annually. In Singapore, lung cancer ranks as the third most common cancer, with 9,732 new cases diagnosed between 2019 and 2023. Despite the addition of PD-L1 checkpoint inhibitors to platinum-based chemotherapy in the first-line setting — a shift that occurred around 2019 — the company noted that approximately 40% of patients experience relapse requiring second-line treatment, and overall survival outcomes remain limited.
The approval adds to a treatment landscape in ES-SCLC that has seen incremental but meaningful change over the past several years. Lurbinectedin as a monotherapy received accelerated approval from the US FDA in 2020 for second-line ES-SCLC based on tumor response rate data; that indication remains under a standard review pathway. The IMforte combination data now provide the basis for a first-line maintenance claim, positioning the combination alongside established induction regimens rather than in the relapsed setting. The ES-SCLC pipeline includes several agents in earlier or parallel development, among them tarlatamab, a DLL3-targeting bispecific T-cell engager from Amgen that received US accelerated approval in the second-line setting in 2024 and is being evaluated in Phase III trials for both confirmatory second-line and first-line maintenance indications. Ifinatamab deruxtecan, a B7-H3-targeting antibody-drug conjugate being developed by Daiichi Sankyo and AstraZeneca, is in Phase III evaluation for second-line ES-SCLC. The lurbinectedin and atezolizumab approval therefore enters a field where multiple mechanistic approaches — transcription inhibition, immune checkpoint blockade, bispecific T-cell engagement, and antibody-drug conjugates — are under active investigation, though few have reached regulatory approval in the first-line maintenance context.