Imfinzi Granted FDA Priority Review for First-Line Treatment of Extensive-Stage Small Cell Lung Cancer

November 30, 2019 News /Bio ValleyBIOON/ --AstraZeneca(AstraZeneca) recently announced that the U.S. Food and Drug Administration (FDA) PD-L1 acceptedTumorSupplemental Biologics License Application (sBLA) for First-Line Treatment of Patients with Extensive-Stage Small Cell Lung Cancer (ES-SCLC) with Immunotherapy Imfinzi (durvalumab) Granted Priority ReviewFDAThe Prescription Drug User Fee Act (PDUFA) target date for the sBLA has been set for the first quarter of 2020. SCLC is an aggressive, fast-growing cancer that, despite an initial response to platinum-based chemotherapy, rapidly relapses and progresses.

This sBLA is based on the positive data from the Phase III CASPIAN trial. The results demonstrated that fixed-dose Imfinzi in combination with standard-of-care (SoC) platinum-based chemotherapy significantly improved overall survival (OS) compared to SoC platinum-based chemotherapy alone. Based on these findings, Imfinzi is the first agent to demonstrate a survival benefit and improved durable responses in patients with extensive-stage small cell lung cancer (ES-SCLC).TumorImmunotherapy.

CASPIAN is a randomized, open-label, multicenter, global Phase III study comparing the efficacy and safety of Imfinzi plus standard-of-care (SoC) platinum-based chemotherapy (etoposide plus cisplatin or carboplatin), Imfinzi plus tremelimumab plus SoC platinum-based chemotherapy, and SoC platinum-based chemotherapy as first-line treatment in patients with extensive-stage small cell lung cancer (ES-SCLC). The Imfinzi plus tremelimumab plus SoC platinum-based chemotherapy regimen is a dual immune checkpoint blockade combined with chemotherapy, consisting of the CTLA-4 checkpoint inhibitor tremelimumab (an anti-CTLA-4 monoclonal antibody), the PD-L1 checkpoint inhibitor Imfinzi (an anti-PD-L1 monoclonal antibody), and SoC chemotherapy. In the study, patients in the experimental arms received up to four cycles of SoC chemotherapy, whereas those in the control arm were allowed to receive up to six cycles of SoC chemotherapy and prophylactic cranial irradiation (PCI). The study was conducted at more than 200 clinical centers across 22 countries, including the United States, Europe, South America, Asia, and the Middle East. The primary endpoint was overall survival (OS).

An interim analysis of a trial conducted by the Independent Data Monitoring Committee (IDMC) concluded that the study had met its primary endpoint. The results demonstrated that, compared with the standard-of-care (SoC) chemotherapy group, the Imfinzi plus SoC chemotherapy group exhibited a 27% reduction in the risk of death (HR=0.73; 95% CI: 0.591–0.909; p=0.0047), a significant prolongation of overall survival (median OS: 13.0 months [11.5, 14.8] vs. 10.3 months [9.3, 11.2]), and a substantially improved 18-month survival rate (33.9% vs. 24.7%).

Furthermore, the Imfinzi plus standard-of-care (SoC) chemotherapy group demonstrated treatment benefits across all efficacy endpoints compared with the SoC chemotherapy alone group, including: a significantly higher progression-free survival (PFS) rate at 12 months (PFS rate: 17.5% vs. 4.7%), a 10.3 percentage-point increase in the confirmed objective response rate (ORR) at 12 months (ORR: 67.9% vs. 57.6%), and a higher proportion of patients with sustained duration of response (DOR) at 12 months (DOR: 22.7% vs. 6.3%). In this study, the safety and tolerability profile of the Imfinzi plus SoC chemotherapy regimen was consistent with that observed in previous studies. Grade 3 or 4 adverse events occurred in 61.5% of patients in the Imfinzi plus SoC treatment group and 62.4% in the SoC chemotherapy group; the proportions of patients discontinuing treatment due to adverse events were similar between the two groups (9.4% vs. 9.4%).

Currently, Imfinzi is also being evaluated in another Phase III clinical trial, ADRIATIC, which assesses the use of Imfinzi following concurrent chemoradiotherapy (CCRT) in patients with limited-stage small cell lung cancer (SCLC).

AstraZenecaTumorJose Baselga, Executive Vice President of Research and Development, previously stated: “The results from the Phase III CASPIAN study are highly encouraging, with more than one-third of patients with small cell lung cancer (SCLC) treated with Imfinzi plus standard-of-care (SoC) chemotherapy still alive at the 18-month milestone. Given the aggressive nature of this disease, these findings are significant. Notably, these results may lead physicians to choose Imfinzi in combination with a cisplatin- or carboplatin-based chemotherapy backbone. We look forward to working closely with regulatory authorities to make Imfinzi available to SCLC patients worldwide as soon as possible.”

Principal Investigator of the CASPIAN Study, University Hospital 12 de Octubre, Madrid, SpainTumorDr. Luis Paz Ares previously stated, “Treatment options for patients with small cell lung cancer (SCLC) are limited; it is a devastating disease with a 5-year survival rate of less than 6%. The robust efficacy data from the CASPIAN study demonstrate that Imfinzi in combination with four cycles of chemotherapy provides a significant survival benefit compared to regimens involving up to six cycles of chemotherapy and prophylactic cranial irradiation (PCI). These data provide evidence and hope for new treatment options for patients with SCLC.”

Lung cancer is the leading cause of cancer-related deaths in both men and women, accounting for approximately one-fifth of all cancer deaths. Lung cancer is broadly classified into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), with SCLC comprising about 15% of cases. Approximately two-thirds of patients with SCLC areDiagnosisExtensive-stage disease, meaning the cancer has spread widely throughout the lungs or to other parts of the body. SCLC is an aggressive, fast-growing cancer that, although initially responsive to platinum-based chemotherapy, relapses and progresses rapidly. The prognosis is particularly poor, with only 6% of SCLC patients surviving five years after diagnosis.

Imfinzi is a PD-L1 immunotherapy that targets and binds to programmed death-ligand 1 (PD-L1), blocking the interaction of PD-L1 with PD-1 and CD80, thereby counteractingTumorimmune evasion strategies and release the suppression of immune responses.

In the field of lung cancer, to date, Imfinzi has been approved in 54 countries worldwide (including the United States, the European Union, and Japan) for the treatment of patients with unresectable locally advanced (Stage III) non-small cell lung cancer (NSCLC). This approval is based on data from the Phase III PACIFIC study. In early September this year, at the American ClinicalTumorData on 3-year overall survival (OS) presented at the American Society of Clinical Oncology (ASCO) Annual Meeting demonstrated durable and sustained OS benefits in patients with unresectable stage III non-small cell lung cancer (NSCLC) who did not experience disease progression after concurrent chemoradiotherapy (CRT): the 3-year OS rate was 57% and median OS was not reached in the Imfinzi group, compared with a 3-year OS rate of 43.5% and a median OS of 29.1 months in the placebo group. Based on these results, Imfinzi became the first immunotherapy proven to confer a 3-year survival benefit in the population with unresectable stage III NSCLC.

Currently, AstraZeneca is conducting a large clinical program to evaluate Imfinzi as monotherapy and in combination with tremelimumab and other agents for NSCLC, SCLC, bladder cancer, head and neck cancer,Liver Cancer, cervical cancer, biliary tract cancer, and other solid tumors. (Bioon.com)

Original Source:Imfinzi granted FDA Priority Review for the treatment of patients with extensive-stage small cell lung cancer