Updated efficacy and predictive biomarkers of QL1706, a bifunctional PD-1/CTLA-4 dual blocker in advanced solid tumors-A phase 1/1b study

QL1706(一种双功能PD-1/CTLA-4双重阻断剂)在晚期实体瘤中的疗效和预测性生物标志物更新——一项1/1b期研究

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Abstract

QL1706 has shown promising efficacy in solid tumors in a phase 1/1b study. Here, we report updated long-term survival outcomes and biomarker analyses. Among 468 patients treated with QL1706 (5 mg/kg), median progression-free survival (mPFS) and overall survival (mOS) are 1.5 and 14.2 months for non-small cell lung cancer (NSCLC), 1.9 and 20.2 months for nasopharyngeal carcinoma (NPC), and 4.2 and 18.6 months for cervical cancer (CC), respectively. Liver metastasis is correlated with poor progression-free survival (PFS) and overall survival (OS) in NSCLC and poor OS in CC, while elevated lactate dehydrogenase is linked to shorter PFS and OS in NPC. CDK4/11q13 diploid or the expression of GZMKhigh & MYClow distinguishes NPCs with the most favorable PFS. In NSCLC, PD-L1+/TIL+ or a low ARG1:CXCL13 ratio indicates better outcomes. QL1706 offers long-term survival benefits in solid tumors, with identified molecular markers aiding in selecting suitable candidates. This study has been registered on clinicaltrials.gov (NCT04296994 and NCT05171790). Keywords: CTLA-4 antibody; bifunctional PD-1; biomarker; cervical cancer; nasopharyngeal carcinoma; non-small cell lung cancer; phase 1 trial.

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