PD-L1表达指导的信迪利单抗与帕博利珠单抗联合或不联合含铂双药化疗治疗未经治晚期非小细胞肺癌患者:一项2期随机对照试验(CTONG1901)

No direct comparison has been performed between different programmed cell death-1(PD-1)inhibitors for first-line treatment in patients with advanced non-small cell lung cancer(NSCLC).The feasibility of using PD-L1-expression-guided immunotherapy remains unknown.In this open-label,phase 2 study(NCT04252365),patients with advanced NSCLC without EGFR or ALK alterations were randomized(1:1)to receive sintilimab or pembrolizumab monotherapy(PD-L1 expression≥50%),or sintilimab or pembrolizumab plus platinum-based chemotherapy(PD-L1 expression<50%).The sample size was calculated by optimal two-stage design.The primary endpoint was the objective response rate(ORR).The study included 71 patients(sintilimab arms,n=35;pembrolizumab arms,n=36)and met its primary endpoint,with a confirmed ORR of 51.4%(18/35)in the sintilimab arms.The confirmed ORR(95%confidence interval)was 46.2%(19.2%,74.9%)and 42.9%(17.7%,71.1%)for patients treated with sintilimab and pembrolizumab monotherapy;and 54.5%(32.2%,75.6%)and 45.4%(24.4%,67.8%)for those treated with sintilimab-and pembrolizumab-based combination therapies.The median progression-free survival was6.9 versus 8.1 months for all sintilimab-treated versus all pembrolizumab-treated patients,respectively,in which it was 7.6 versus 11.0 months in monotherapy and 7.4 versus 7.1 months in combination therapies.The median overall survival was 14.9 versus 21.3 months for all sintilimab-treated versus all pembrolizumab-treated patients,respectively,in which it was 14.9 versus 22.6 months in monotherapy and 14.7 versus 17.3 months in combination therapies.Treatment-related adverse events were consistent with safety outcomes of monotherapy and combination therapy in previous phase III studies.However,the incidence of rash was higher with sintilimab than pembrolizumab monotherapy.This is the first prospective phase 2 study to directly compare two anti-PD-1 antibodies as first-line treatment in advanced NSCLC.Sintilimab was efficacious and well-tolerated irrespective of PD-L1 expression level in patients with advanced NSCLC and had similar efficacy and safety to pembrolizumab.

Ultrafine Cu nanoclusters confined within covalent organic frameworks for efficient electroreduction of CO_(2) to CH_(4) by synergistic strategy

Electrocatalytic CO_(2) reduction(ECR)to high value-added chemicals by using renewable electricity presents a promising strategy to realize“carbon neutrality”.However,the ECR system is still limited by its low current density and poor CO_(2) utilization efficiency.Herein,by using the confinement effect of covalent organic frame-works(COFs)to confine the in-situ growth of metal nanoclusters(NCs),we develop a series of Cu NCs encap-sulated on COF catalysts(Cu-NC@COF)for ECR.Among them,Cu-NC@CuPc-COF as a gas diffusion electrode(GDE)achieves a maximum CO_(2)-to-CH_(4) Faradaic efficiency of 74±3%(at-1.0 V vs.Reversible Hydrogen Electrode(RHE))with a current density of 538±31 mA cm^(-2)(at-1.2 V vs.RHE)in a flow cell,making it one of the best among reported materials.More importantly,the current density is much higher than the relevant industrial current density(200 mA cm^(-2)),indicating the potential for industrial application.This work opens up new possibilities for the design of ECR catalysts that utilize synergistic strategy.