Danvatirsen（STAT3靶向反义寡核苷酸）联合帕博利珠单抗对比帕博利珠单抗治疗复发/转移性头颈部鳞癌（PEMDA-HN）：随机2期试验
Danvatirsen plus pembrolizumab versus pembrolizumab for recurrent and/or metastatic head and neck squamous cell carcinoma (PEMDA-HN): a randomized, phase 2 trial
STAT3蛋白被认为会促进肿瘤形成有利的微环境，本研究测试用靶向STAT3的反义寡核苷酸（一种能抑制特定基因表达的短链核酸药物）danvatirsen联合帕博利珠单抗作为复发/转移性头颈部鳞癌一线治疗。这是该联合方案的首个随机试验，69例患者按2:1随机接受联合治疗或帕博利珠单抗单药。结果显示两组客观缓解率分别为15.6%和14.3%，无显著差异，且联合组不良反应更多；因缺乏疗效研究提前停止入组。结论是该联合方案未能优于单药，STAT3靶向策略仍需进一步探索。
为什么推荐给您：STAT3靶向反义寡核苷酸联合免疫治疗的首次随机试验，但结果阴性，属值得关注。
不需要生物学背景，多打比方
正在获取全文并生成讲解（拿不到全文就依据摘要），大约需要 30–60 秒…
已等待 0 秒
这篇还没有动画
动画会把研究的流程、作用机制和关键结果一步一步演示出来，每一步都标明出自原文哪里。制作大约需要 30–60 秒。
摘要Abstract
PURPOSE: STAT3 is important in promoting a pro-oncogenic tumor microenvironment. This first randomized trial of a STAT3-targeting ASO with pembrolizumab assessed whether this first-line combination would improve outcomes compared with pembrolizumab alone in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).
PATIENTS AND METHODS: This multicenter, randomized, open-label, controlled study (NCT05814666) enrolled patients with previously untreated R/M-HNSCC with positive PD-L1 expression (combined positive score [CPS] ≥1). Patients were stratified by CPS (1-19; ≥20) and randomized 2:1 to danvatirsen 3mg/kg IV weekly (with 2 loading doses in week 1) plus pembrolizumab 200mg IV every 3 weeks or pembrolizumab alone. Patients received 21-day treatment cycles until progressive disease, unacceptable toxicity, or voluntary withdrawal. Primary endpoint was overall response rate (ORR: partial + complete response per RECIST-v1.1).
RESULTS: 69 patients were randomized and 66 treated (51 [77.3%] male), 45 with danvatirsen + pembrolizumab, 21 with pembrolizumab alone. Enrolment was stopped due to lack of response in the CPS 1-19 cohort after ≥1 scan (~6 weeks of treatment) and in the CPS ≥20 cohort after ≥2 scans (~12 weeks). In the final analysis, ORRs were 15.6% and 14.3%, respectively (risk difference 1.3, P=1.0). The treatment-emergent adverse-event rate was increased in the combination arm (97.8% vs 85.7%), and the combination side effect profile was similar to previous danvatirsen studies.
CONCLUSIONS: Combination danvatirsen + pembrolizumab did not improve ORR compared to pembrolizumab alone in first-line treatment of R/M-HNSCC. Further exploration of STAT3-targeted approaches is needed within the context of immunotherapy.