Immunotherapy for lung cancer! AstraZeneca immunofinzi + tremelimumab immune combination first-line treatment of phase III clinical failure

August 23, 2019 / bioun / -- AstraZeneca, a British pharmaceutical giant, recently announced the final overall survival (OS) results of Neptune, a phase III clinical study of PD-L1 tumor immunotherapy for imfinzi (durvalumab) lung cancer This study is a randomized, open label, multicenter, global phase III study in patients with stage IV (metastatic) non-small cell lung cancer (NSCLC) who have not been treated before The study population includes patients with non squamous or squamous histology, patients without EGFR or ALK mutations, and patients with various PD-L1 expression levels The primary end point was overall survival (OS) in patients with high tumor mutation burden (TMB) In the study, more than 200 clinical centers in 29 countries around the world, including the United States, Europe, South America and Central America, the Middle East and Asia TMB is a measure of the number of mutations in the tumor genome (DNA) High blood TMB means 20 or more mutations (≥ 20mut / MB) per megabase The results showed that in patients with high TMB, compared with standard care (SOC) chemotherapy, the combination of imfinzi and tremelimumab failed to improve OS and did not reach the main end point of the study In this study, the safety and tolerance of the combination of imfinzi and tremelimumab were consistent with the previous studies The full data of the study will be released at the upcoming medical conference "We are in-depth analyzing a large number of clinical and biomarker data from this study to gain further insights and improve the immunooncology treatment of patients with metastatic NSCLC," said Jos ou baselga, executive vice president of cancer research and development at AstraZeneca Imfinzi (durvalumab) is a kind of PD-L1 immunotherapy, targeting to bind to programmed cell death factor ligand 1 (PD-L1), blocking the interaction of PD-L1 with PD-1 and CD80, antagonizing the immune escape strategy of tumor and releasing the inhibition of immune response At present, AstraZeneca is carrying out a large-scale clinical project, in which part of the research is evaluating the single drug therapy of imfinzi and the combination therapy of tremelimumab for the first-line treatment of solid tumors such as NSCLC, small cell lung cancer, locally advanced or metastatic urothelial cancer, head and neck cancer In lung cancer, imfinzi has been approved by 49 countries in the world for the treatment of unresectable stage III NSCLC At present, AstraZeneca is carrying out a series of phase III studies to evaluate the potential of imfinzi in the treatment of stage IV NSCLC, including the first-line treatment of phase III study Pearl (imfinzi single drug vs SOC chemotherapy) and Poseidon (imfinzi + chemotherapy, imfinzi + tremelimumab + chemotherapy vs SOC chemotherapy) In July this year, the U.S FDA approved to update the U.S prescription information of imfinzi in the treatment of unresectable stage III NSCLC patients who did not progress after receiving the platinum containing concurrent radiotherapy and chemotherapy (CRT), and included the total survival time (OS) data of stage III clinical study Pacific Two years OS analysis results of this label update: regardless of the expression of PD-L1, after CRT, patients receiving imfinzi treatment had significant and clinically proven OS benefits compared with placebo group: imfinzi reduced the risk of death by 32% compared with placebo (HR = 0.68, 95% CI: 0.53-0.87; P = 0.0025) In a three-year follow-up post event OS analysis published at the ASCO annual meeting in 2019, the results of imfinzi were consistent with the data at the two-year time point, showing that imfinzi reduced the risk of death by 31% compared with placebo (HR = 0.69, 95% CI: 0.55-0.86) After three years of follow-up, 57% (95% CI: 52.3-61.4) of the patients in the imfinzi treatment group were still alive, and the median OS was not yet reached 44% (95% CI: 37.0-49.9) of the patients in the placebo group were still alive, and the median OS was 29.1 months NSCLC in stage III (local advanced stage) is usually divided into three subclasses (IIIA, IIIB, IIIc), which are defined by the extent of tumor local spread and the possibility of surgery Stage III is different from stage IV, in which cancer has spread (metastasized) to distant organs, and the current stage III treatment is aimed at curing It is estimated that stage III NSCLC accounts for about one third of NSCLC Most of the patients with stage III NSCLC were diagnosed as non resectable tumor The former standard treatment was chemotherapy and radiotherapy (CRT), and then actively monitored the progress of the disease But the prognosis of this disease is not ideal, and the long-term survival rate is very low It is worth mentioning that imfinzi is the only tumor immunotherapy approved for the treatment of stage III NSCLC patients after radiotherapy and chemotherapy (CRT) Source: update on the phase III Neptune trial of imfinzi plus tremelimumab in stage IV non small cell lung cancer