AstraZeneca's Imfinzi Demonstrates Significant Survival Benefit in First-Line Treatment of Extensive-Stage Small Cell Lung Cancer

March 18, 2020/BioValleyBIOON/--AstraZeneca(AstraZeneca) recently announced high-level results from the final analysis of the Phase III CASPIAN study (NCT03043872), evaluating Imfinzi (Imfinzi, generic name: durvalumab), an anti-PD-L1 therapy, in combination with standard of care (SoC) platinum-based chemotherapy as first-line treatment for patients with extensive-stage small cell lung cancer (ES-SCLC). The data demonstrated that Imfinzi plus SoC platinum-based chemotherapy provided a sustained and clinically meaningful overall survival (OS) benefit.

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 carboplatin or cisplatin), 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 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).

In June 2019, the CASPIAN trial met one of its primary endpoints: a pre-planned interim analysis conducted by the Independent Data Monitoring Committee (IDMC) showed that,Compared with SoC, Imfinzi plus SoC demonstrated statistically significant and clinically meaningful improvements in OS.. Specific data were as follows: compared with the SoC group, the Imfinzi + SoC group27% Reduction in Mortality Risk（HR=0.73，95%CI:0.591-0.909，p=0.0047）、Significant Prolongation of Overall Survival(median OS: 13.0 months [11.5, 14.8] vs 10.3 months [9.3, 11.2]),Significant Increase in 18-Month Survival Rate(33.9% vs 24.7%). Furthermore,Imfinzi + SoC group demonstrated therapeutic benefit over the SoC group across all efficacy endpoints, including: a significantly improved 12-month progression-free survival rate (PFS rate: 17.5% vs. 4.7%), a 10.3% increase in the 12-month confirmed objective response rate (ORR: 67.9% vs. 57.6%), and an increased 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 Imfinzi plus standard-of-care (SoC) chemotherapy was consistent with 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 proportion of patients discontinuing treatment due to adverse events was similar between the two groups (9.4% vs. 9.4%).

Based on the study results,Imfinzi is the first to demonstrate survival benefit and improved durable response in patients with ES-SCLCTumorImmunotherapy.However, it is worth noting that in the final analysis, the Imfinzi + tremelimumab + SoC regimen did not meet the primary endpoint of statistically significant improvement in OS compared to SoC. In this study, the safety and tolerability of Imfinzi and tremelimumab were consistent with the known safety profiles of these drugs. These data will be presented at an upcoming medicalConferencepublished above.

AstraZenecaTumorJosé Baselga, Executive Vice President of Research and Development, stated, “We are pleased to see the sustained and meaningful survival benefit of Imfinzi in patients with small cell lung cancer after a median follow-up of more than two years. Currently, the regimen of Imfinzi plus standard of care (etoposide plus carboplatin or cisplatin) has received the world’s first regulatory approval in Singapore as first-line treatment for extensive-stage small cell lung cancer. We will continue to pursue approvals from additional regulatory authorities to provide patients with an important new first-line treatment option.”

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%. 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, rapidly growing cancer that, although initially responsive to platinum-based chemotherapy, relapses and progresses quickly. The prognosis is particularly poor, with only 6% of SCLC patients surviving five years after diagnosis.

Imfinzi (durvalumab) is a humanized PD-L1 monoclonal antibody that blocks the binding of PD-L1 to PD-1 and CD80, thereby blockingTumorImmune escape and release of suppressed immune responses. To date, Imfinzi has been approved in more than 60 countries (including the United States, Japan, China, and the entire European Union) for the curative treatment of patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent chemoradiotherapy with platinum-based chemotherapy. In addition, Imfinzi has also been approved in more than 10 countries, including the United States, for the treatment of patients with advanced bladder cancer who have previously received platinum-containing chemotherapy.

Just recently, based on data from the Phase III CASPIAN trial, Imfinzi in combination with standard of care (SoC) chemotherapy as first-line treatment for extensive-stage small cell lung cancer (ES-SCLC) received its first global regulatory approval in Singapore. The application for this indication is currently under review by regulatory authorities in the United States, the European Union, and Japan. In the United States,FDAPriority review has been granted for this indication application, with the Prescription Drug User Fee Act (PDUFA) target date set for the first quarter of 2020.

As part of the extensive development program for lung cancer, Imfinzi is also being evaluated in another Phase III clinical study, ADRIATIC, which assesses the use of Imfinzi following concurrent chemoradiotherapy (CCRT) in patients with limited-stage small cell lung cancer (SCLC). Data from this study are expected to be available in 2021.

Tremelimumab is a human monoclonal antibody that targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), blocking CTLA-4 activity, promoting T-cell activation, and initiatingTumorImmune response, promoting cancer cell death. Tremelimumab and Bristol-Myers Squibb’s marketed antibody drug Yervoy (ipilimumab) target the same checkpoint, CTLA-4.

Currently, AstraZeneca is conducting a large-scale 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 confirmed a sustained overall survival benefit in final analysis of the Phase III CASPIAN trial in 1st-line extensive-stage small cell lung cancer