High-level results from the final analysis of the Phase III CASPIAN trial showed AstraZeneca’s Imfinzi (durvalumab) in combination with a choice of standard-of-care (SoC) chemotherapies confirmed a sustained, clinically meaningful overall survival (OS) benefit for patients with extensive-stage small cell lung cancer (ES-SCLC) treated in the 1st-line setting.
In June 2019, the CASPIAN trial met one primary endpoint for Imfinzi plus SoC (etoposide and either carboplatin or cisplatin chemotherapy) by demonstrating a statistically significant and clinically meaningful improvement in OS versus SoC alone at a planned interim analysis.
The second experimental arm testing tremelimumab, an anti-CTLA4 monoclonal antibody, added to Imfinzi and SoC did not meet its primary endpoint of demonstrating a statistically significant improvement in OS in this analysis.
“We are pleased to see the sustained and meaningful survival benefit of Imfinzi for patients with small cell lung cancer after more than two years median follow up. We have already received the first global regulatory approval for Imfinzi with etoposide plus either carboplatin or cisplatin and remain on track for more approvals soon as we provide patients an important new 1st-line treatment option,” José Baselga, Executive Vice President, Oncology R&D, said.
The safety and tolerability for Imfinzi and tremelimumab were consistent with the known safety profiles of these medicines. The data will be presented at a forthcoming medical meeting.
Imfinzi in combination with etoposide and either carboplatin or cisplatin is currently under regulatory review for the treatment of ES-SCLC in the 1st-line setting based on the Phase III CASPIAN trial in the US, EU and Japan. The US Food and Drug Administration has granted a Priority Review with a Prescription Drug User Fee Act date set for the first quarter of 2020.
As part of a broad development program, Imfinzi is also being tested following concurrent chemoradiation therapy in patients with limited-stage SCLC in the Phase III ADRIATIC trial with data anticipated in 2021.
Lung cancer is the leading cause of cancer death among both men and women and accounts for about one-fifth of all cancer deaths. Lung cancer is broadly split into non-small cell lung cancer (NSCLC) and SCLC, with about 15% classified as SCLC. SCLC is a highly aggressive, fast-growing form of lung cancer that typically recurs and progresses rapidly despite initial response to chemotherapy. About two thirds of SCLC patients are diagnosed with extensive-stage disease, in which the cancer has spread widely through the lung or to other parts of the body. Prognosis is particularly poor, as only 6% of all SCLC patients will be alive five years after diagnosis.
CASPIAN is a randomized, open-label, multi-center, global, Phase III trial in the 1st-line treatment of 805 patients with ES-SCLC. The trial compared Imfinzi in combination with etoposide and either carboplatin or cisplatin chemotherapy, or Imfinzi and chemotherapy with the addition of a second immunotherapy, tremelimumab, versus chemotherapy alone. In the experimental arms, patients were treated with four cycles of chemotherapy. In comparison, the control arm allowed up to six cycles of chemotherapy and optional prophylactic cranial irradiation. The trial was conducted in more than 200 centers across 23 countries, including the US, in Europe, South America, Asia and the Middle East. The primary endpoint was OS in each of the two experimental arms.
Imfinzi (durvalumab) is a human monoclonal antibody that binds to PD-L1 and blocks the interaction of PD-L1 with PD-1 and CD80, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.
Imfinzi is approved in the curative-intent setting of unresectable, Stage III NSCLC after chemoradiation therapy in the US, Japan, China, across the EU and in many other countries, based on the Phase III PACIFIC trial. Imfinzi recently received its first global approval for the 1st-line treatment of ES-SCLC in combination with SoC chemotherapy in Singapore. Imfinzi is also approved for previously treated patients with advanced bladder cancer in the US and a small number of other countries.
As part of a broad development program, Imfinzi is also being tested as a monotherapy and in combination with tremelimumab, an anti-CTLA4 monoclonal antibody and potential new medicine, as a treatment for patients with NSCLC, SCLC, bladder cancer, head and neck cancer, liver cancer, biliary tract cancer, cervical cancer and other solid tumors.
Tremelimumab is a human monoclonal antibody and potential new medicine that targets the activity of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Tremelimumab blocks the activity of CTLA-4, contributing to T cell activation, priming the immune response to cancer and fostering cancer cell death. Tremelimumab is being tested in a clinical trial program in combination with Imfinzi in NSCLC, SCLC, bladder cancer, head and neck cancer and liver cancer.
