"Second-generation PD-1" helps patients with advanced non-small cell lung cancer survive in the long term.

The reason why m7824 is called an upgraded PD-1 inhibitor is that it combines anti TGF - β receptor and anti-PD-L1 monoclonal antibody.on the one hand, it can recognize the antibody structure binding to PD-L1, and on the other hand, it can recognize the receptor binding to TGF - β, which can block tumor cells from escaping immune regulation from two different pathways, leaving tumor cells helpless.thus greatly increasing treatment efficiency, which is also known as "second generation" PD-1 or "upgraded" PD-1 inhibitors.recently, the clinical trial results of m7824 as a second-line treatment for non-small cell lung cancer (NSCLC) were published: the response rate of m7824 was 21.3%, which exceeded the objective response rate (ORR) of 19.4% of pabolizumab [1].except for PD-L1 negative patients, the survival time of the other subgroups treated with m7824 was longer than 24 months.nct02517398 is a multicenter, open label phase 1 clinical trial. 80 patients with advanced NSCLC were enrolled.they had received platinum dual therapy or platinum therapy, but did not receive adjuvant or neoadjuvant immunotherapy when their condition progressed.the patients were randomly divided into two groups, one group took m7824 orally every two weeks, the dose was 500mg; the other group took the recommended dose of 1200mg.subsequently, the objective response rate (ORR) of the patients was evaluated to investigate whether m7824 was effective in patients with naclc.the results published in the study design have been observed for a long time, and half of the patients have been observed for more than one year. The specific results are as follows: it is more popular than drug K. The results show that 21.3% of patients (17 / 80) have significantly reduced tumor lesions (median follow-up period is about 12 months), and the curative effect has been maintained for a long time.two fifths of patients are under control.compared with the low-dose group of 500 mg, the normal dose of 1200 mg had more patients with remission (25.0% vs 17.5%), and the orr of the general population was 21.3%, which was higher than that of the famous drug K, with an Orr of 19.4% (median follow-up period of 10.9 months).the effect lasted for more than 14 months in more than half of the patients, and one eighth of the patients were still under treatment.it has a more extensive effect on PD-L1 positive patients. At the dose of 1200 mg, m7824 can alleviate 37% of patients with PD-L1 positive (tumor cell expression ≥ 1%). For patients with strong expression of PD-L1 (expression ≥ 80%), the remission rate is as high as 86%.half of PD-L1 positive patients had disease-free survival of more than 9.5 months, while patients with strong expression of PD-L1 increased to 15.2 months.35.4% of PD-L1 positive patients and 68.6% of PD-L1 overexpression patients had disease-free survival for 12 months.half of PD-L1 negative patients have survived for more than 12.2 months. because the mortality of PD-L1 positive patients is low, the survival data of PD-L1 positive patients is still to be counted in follow-up trials. compared with the safety of different dose groups, the incidence of adverse events related to m7824 treatment was 55 / 80 (69%), and the incidence of serious adverse events was 29%. of the 80 patients, 8 (10%) had severe treatment-related adverse events leading to treatment discontinuation. immunotherapy has brought about a radical change in the treatment of advanced cancer, and some patients have achieved "cure" because of it. however, the single drug effective rate of immuno tumor drugs is not high. in order to make more patients respond to immunotherapy, many clinical trials are evaluating the combination of anti PD-1 / PD-L1 drugs with other therapies. however, the combination of drugs may bring cumulative toxicity and limit its clinical application. the clinical data of m7824 are gratifying. At present, the drug has also carried out clinical trials of other tumors, including gastric cancer, biliary cancer, esophageal cancer, etc. in addition, m7824 is also carrying out a comparative study with K drug (clinical trial No.: nct03631706). We will wait and see the efficacy of one line to head PK! References E.B. Garon, N.A. Rizvi, R. Hui, et al al.Pembrolizumab For the treatment of non-small-cell lung cancer. N Engl J Med, 372 (2015), pp. 2018-2028 code scanning consultation search focus: Oncogene detection | clinical recruitment | patient communication