공시 • Apr 21
Specialised Therapeutics Announces Approval of Zepzelca in Combination with Atezolizumab as First-Line Maintenance Treatment for Extensive-Stage Small Cell Lung Cancer in Australia and Singapore
Specialised Therapeutics welcomed the approval of ZEPZELCA (lurbinectedin), in combination with atezolizumab (Tecentriq), as a new first-line maintenance treatment option for adult patients in Australia and Singapore, who have been diagnosed with extensive-stage small cell lung cancer (ES-SCLC), an aggressive form of lung cancer. In combination with atezolizumab, ZEPZELCA has been approved for use in Australia and Singapore as a maintenance treatment for extensive-stage small cell lung cancer (ES-SCLC) in adult patients whose disease has not progressed after first-line induction therapy with atezolizumab, carboplatin and etoposide. Both approvals for ZEPZELCA in ES-SCLC were obtained under Project Orbis — an initiative of the United States Food and Drug Administration's (US FDA's) Oncology Center of Excellence. These ZEPZELCA approvals represent the eighth time Specialised Therapeutics has successfully navigated the Project Orbis process since 2021. Lung cancer remains a significant health challenge in the region, with an estimated 15,000 diagnoses and 9,000 deaths from the disease each year in Australia. In Singapore, lung cancer is the third most common cancer, with 9,732 new cases diagnosed between 2019-2023. Small cell lung cancer (SCLC) is a highly aggressive cancer that has often already spread to other organs when first diagnosed. It accounts for approximately 10-15% of all lung cancer cases and has a low 5-year survival rate of under 7%. ZEPZELCA is being made available in Australia, New Zealand, Singapore, Malaysia, Thailand and Vietnam by Specialised Therapeutics, under exclusive license from European biopharmaceutical company PharmaMar. ZEPZELCA belongs to a class of medicines known as alkylating agents, which work by damaging the DNA of cancer cells, helping to slow or stop their growth. The regulatory approvals for ES-SCLC in Australia and Singapore were based on results from the Phase 3 IMforte clinical trial. The study enrolled 660 treatment-naïve patients with ES-SCLC across 13 countries in the induction phase. Following this, 483 patients who responded to induction treatment were randomised to receive either ZEPZELCA with atezolizumab (LU-AT) or atezolizumab monotherapy (AT) as first-line maintenance therapy. The trial results supported the use of LU-AT as a new first-line maintenance treatment option over AT alone in patients with this aggressive cancer, with improvements recorded in both median progression free survival (PFS; 5.4 months vs. 2.1 months) and median overall survival (OS; 13.2 months vs.10.6 months). Significant variations in treatment-related adverse events (AEs) were noted in the two trial groups (83.5% in patients receiving LU-AT vs. 40% among patients receiving AT monotherapy). Treatment with LU-AT was considered to be generally well tolerated, with no new or unexpected safety signals. The most common adverse reactions (= 30%), including laboratory abnormalities, in patients who received ZEPZELCA with atezolizumab were decreased lymphocytes, decreased platelets, decreased haemoglobin, decreased leukocytes, decreased neutrophils, nausea, and fatigue/asthenia. ZEPZELCA (lurbinectedin), also known as PM1183, is an analog of the marine compound ET-736 isolated from the sea squirt Ecteinascidia turbinata in which a hydrogen atom has been replaced by a methoxy group. It is a selective inhibitor of the oncogenic transcription programs on which many tumours are particularly dependent. Together with its effect on cancer cells, ZEPZELCA inhibits oncogenic transcription in tumour-associated macrophages, downregulating the production of cytokines that are essential for the growth of the tumour. Transcriptional addiction is an acknowledged target in those diseases, many of them lacking other actionable targets. In Australia and Singapore, ZEPZELCA is indicated for the treatment of patients with metastatic small cell lung cancer (SCLC) that has progressed on or after prior platinum-containing therapy. The IMforte clinical trial was a randomised, multicentre, open-label, Phase 3 trial of 660 treatment-naive patients with ES-SCLC conducted across 96 hospitals and medical centres in 13 countries, including Belgium, Germany, Greece, Hungary, Italy, Mexico, Poland, South Korea, Spain, Taiwan, Türkiye, the UK and the US. The trial evaluated the efficacy and safety of lurbinectedin (ZEPZELCA) combined with atezolizumab (Tecentriq) as first-line maintenance therapy (LU-AT), compared to treatment with atezolizumab alone (AT) for patients with ES-SCLC, following first-line induction therapy with atezolizumab, carboplatin and etoposide. Of the 660 enrolled patients, 483 were randomised to receive treatment with LU-AT (n=242) or AT monotherapy (n=241). The IMforte trial demonstrated that treatment with LU-AT as a first line regimen offers clinical advantages over AT alone in patients with ES-SCLC, with significant improvements to median progression-free survival (PFS; 5.4 months vs. 2.1 months) and median overall survival (13.2 months vs.10.6 months) observed. Treatment-related adverse events (AEs) occurred in 83.5% of patients who received LU-AT, compared with 40% in the AT arm. This variation was observed in patients who experienced a grade 3/4 AE (25.6% vs. 5.8%), a grade 5 AE (0.8% vs. 0.4%) and AEs that led to treatment discontinuation (6.2% vs. 3.3%). However, treatment with LU-AT was considered to be generally well tolerated, with no new or unexpected safety signals. The trial results suggest that LU-AT may serve as a novel first-line maintenance treatment option for patients with ES-SCLC.
