10 September 2023 ● IMbrella A, an extension of the Phase III IMpower133 study, demonstrates the potential for a durable overall survival benefit with Tecentriq plus chemotherapy in extensive-stage small cell lung cancer (ES-SCLC) ● IMbrella A data build on the previously reported IMpower133 trial, which was the first clinically meaningful advance in the treatment of ES-SCLC in more than twenty years 10 September 2023 - Results presented today from the Phase III IMpower133 study and extension trial IMbrella A, show Roche’s Tecentriq® (atezolizumab), in combination with chemotherapy, demonstrates a potential long-term overall survival (OS) benefit as first-line treatment for extensive-stage small cell lung cancer (ES-SCLC). As presented at the IASLC 2023 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer, these are the first reported five-year survival outcomes for people who have received first-line cancer immunotherapy and chemotherapy. Data from IMbrella A and IMpower133 represent the longest survival follow-up data ever reported for a cancer immunotherapy combination in ES-SCLC. At this five-year OS landmark in IMpower133/IMbrella A, 12% of patients receiving Tecentriq were still alive, demonstrating the potential for a durable survival benefit with Tecentriq plus chemotherapy. 1 Historical data of platinum-etoposide chemotherapy, which was the standard first-line treatment for ES-SCLC for several decades, show a five-year OS rate of approximately 2%. 2,3 These results build on the previously reported IMpower133 study. The primary results reported in June 2018 showed that Tecentriq plus chemotherapy helped people live significantly longer compared with chemotherapy alone (median OS=12.3 versus 10.3 months; hazard ratio [HR]=0.70, 95% CI: 0.54-0.91; p=0.0069). These findings were the first clinically meaningful advance in the treatment of ES-SCLC in more than twenty years. 4 “The results of IMbrella A and IMpower133 represent the longest survival follow-up reported to date for people with ES-SCLC who have received cancer immunotherapy,” said Dr Stephen Liu, MD, Associate Professor of Medicine, Director of Thoracic Oncology and Head of Developmental Therapeutics at the Lombardi Comprehensive Cancer Center, Georgetown University. “The five-year survival rate of 12% is an important landmark for patients with ES-SCLC who have historically had poor outcomes with a five-year survival rate of approximately 2%.” Safety data for Tecentriq were consistent with the known safety profile and no new safety signals were identified. Following the primary results of IMpower133, Tecentriq plus chemotherapy became the first cancer immunotherapy combination approved for ES-SCLC in more than 100 countries and reimbursed in more than 30 countries. The Tecentriq combination has been adopted as a standard of care in multiple clinical practice guidelines globally, including in the ESMO Clinical Practice Guidelines. 5 The IMbrella A study is an open-label, non-randomised, multicentre extension study for several Roche/Genentech-sponsored Tecentriq trials, including IMpower133. At the IASLC 2023 World Conference on Lung Cancer, results from patients who rolled over from IMpower133 were reported. At the time of the IMpower133 study closure, patients in the experimental arm of IMpower133 were offered the option to enrol into IMbrella A. In total, 18 patients rolled over from IMpower133 to IMbrella A, therefore interpretation of the data should take into consideration the small sample size. 1 IMpower133 is a Phase III, multicentre, double-blinded, randomised placebo-controlled study evaluating the efficacy and safety of Tecentriq in combination with chemotherapy (carboplatin and etoposide) versus chemotherapy (carboplatin and etoposide) alone in chemotherapy-naïve adults with ES-SCLC. The study randomised 403 people at a ratio of 1:1 to receive either Tecentriq in combination with carboplatin and etoposide, or placebo in combination with carboplatin and etoposide. The co-primary endpoints were progression-free survival (PFS), as determined by the investigator using RECIST v1.1, and OS in the intention-to-treat population. 4,6 At a median follow-up of 13.9 months, Tecentriq in combination with chemotherapy was shown to help people with ES-SCLC live significantly longer, compared with chemotherapy alone (OS=12.3 versus 10.3 months; HR=0.70, 95% CI: 0.54-0.91, p=0.0069). The Tecentriq-based combination also significantly reduced the risk of disease worsening or death compared with chemotherapy alone (PFS=5.2 versus 4.3 months; HR=0.77; 95% CI: 0.62–0.96, p=0.017). Safety data for the Tecentriq and chemotherapy combination were consistent with the known safety profile of Tecentriq. 4,6 Lung cancer is one of the leading causes of cancer death globally. 7 Each year 1.8 million people die as a result of the disease; this translates into more than 4,900 deaths worldwide every day. 8 Lung cancer can be broadly divided into two major types: non-small cell lung cancer (NSCLC) and SCLC. SCLC is the second most common type of lung cancer, after NSCLC, and accounts for approximately 10-15% of lung cancer diagnoses. 9 An estimated 260,000 new cases of SCLC were diagnosed worldwide in 2015. 10 SCLC has the most aggressive course of any lung cancer and is associated with a worse prognosis than NSCLC. 11 Tecentriq is a cancer immunotherapy approved for some of the most aggressive and difficult-to-treat forms of cancer. Tecentriq was the first cancer immunotherapy approved for the treatment of a certain type of early-stage NSCLC, SCLC and hepatocellular carcinoma. Tecentriq is also approved in countries around the world, either alone or in combination with targeted therapies and/or chemotherapies, for various forms of metastatic NSCLC, certain types of metastatic urothelial cancer, PD-L1-positive metastatic triple-negative breast cancer and BRAF V600 mutation-positive advanced melanoma. Tecentriq is a monoclonal antibody designed to bind with a protein called programmed death ligand-1 (PD-L1), which is expressed on tumour cells and tumour-infiltrating immune cells, blocking its interactions with both PD-1 and B7.1 receptors. By inhibiting PD-L1, Tecentriq may enable the activation of T-cells. Tecentriq is a cancer immunotherapy that has the potential to be used as a foundational combination partner with other immunotherapies, targeted medicines and various chemotherapies across a broad range of cancers. In addition to intravenous infusion, the formulation of Tecentriq is also being investigated as a subcutaneous injection to help address the growing burden of cancer treatment for patients and healthcare systems. Lung cancer is a major area of focus and investment for Roche, and we are committed to developing new approaches, medicines and tests that can help people with this deadly disease. Our goal is to provide an effective treatment option for every person diagnosed with lung cancer. We currently have six approved medicines to treat certain kinds of lung cancer and more than ten medicines being developed to target the most common genetic drivers of lung cancer or to boost the immune system to combat the disease. Founded in 1896 in Basel, Switzerland, as one of the first industrial manufacturers of branded medicines, Roche has grown into the world’s largest biotechnology company and the global leader in in-vitro diagnostics. The company pursues scientific excellence to discover and develop medicines and diagnostics for improving and saving the lives of people around the world. We are a pioneer in personalised healthcare and want to further transform how healthcare is delivered to have an even greater impact. To provide the best care for each person we partner with many stakeholders and combine our strengths in Diagnostics and Pharma with data insights from the clinical practice. In recognising our endeavour to pursue a long-term perspective in all we do, Roche has been named one of the most sustainable companies in the pharmaceuticals industry by the Dow Jones Sustainability Indices for the thirteenth consecutive year. This distinction also reflects our efforts to improve access to healthcare together with local partners in every country we work. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com .

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