KRAS / RAS 靶向 — 从平台化到 Ph3 验证
发生了什么
AACR 2026会议上报告的CheckMate 77T试验(CT015)显示,围手术期纳武利尤单抗无论患者基线ctDNA状态、术前ctDNA清除情况还是MRD状态如何,均能延长EFS[1]。机器学习模型进一步确认,ctDNA清除、非N2分期、鳞状组织学类型及纳武利尤单抗治疗与EFS获益相关,而KEAP1、SMARCA4、CDKN2A突变则不相关[2]。据报道,术前ctDNA清除率在纳武利尤单抗组显著高于对照组,且清除与EFS获益相关[3]。
为什么重要
这一结果强化了ctDNA动态监测作为围手术期免疫治疗获益预测生物标志物的地位,同时提示部分常见驱动基因突变不影响纳武利尤单抗疗效。这为监管审评生物标志物分层策略、临床医生制定新辅助/辅助治疗方案以及BD评估CheckMate 77T资产差异化价值提供了关键依据。
还缺什么
尚需完整公开的风险比、置信区间、P值及ctDNA/MRD检测技术细节。后续关键节点包括更长随访的总生存数据、与含化疗新辅助免疫联合方案的头对头比较、机器学习模型在独立队列的前瞻验证,以及监管机构对ctDNA指导治疗决策的接受度。
- 1.AACR 2026: Clinical outcomes by genomic markers and ... · clin.larvol.com 2026
- 2.Biomarkers of nivolumab benefit in resectable non-small ... · nature.com 2026
- 3.Circulating tumor DNA (ctDNA) in early-stage NSCLC · oaepublish.com 2026
ctDNA + genomics finally refining perioperative IO in resectable NSCLC 👀
#AACR26
CheckMate 77T – exploratory biomarker analysis
🧬 Population
Resectable stage IIA–IIIB (N2) NSCLC
NIVO + chemo → surgery → adjuvant NIVO vs placebo
🧪 Key genomic group
KEAP1 / STK11 / CDKN2A / SMARCA4 alterations
⚡ Key findings
✅ Genomically “high-risk” tumors benefit MORE
• EFS HR 0.48 (95% CI 0.28–0.83)
• 30-mo EFS 60% vs 30%
❗ No alterations → limited differential benefit
• HR 0.90
🧬 ctDNA matters
• Detectable baseline ctDNA → NIVO benefit (HR 0.58)
• MRD-negative post-surgery → trend favoring NIVO
🎯 Key predictors of better EFS
• pCR
• ctDNA clearance before surgery
• Receipt of NIVO
• Definitive surgery
🧠 Big insight
Genomic alterations linked to IO resistance in advanced disease
➡️ may NOT predict resistance in early-stage
➡️ may identify patients deriving greater perioperative benefit
🔥 Clinical takeaway
Perioperative NIVO works across genomics,
but ctDNA dynamics + high-risk mutations may enrich responders
📖 Full data from CheckMate 77T biomarker analysis
@OncoAlert @myesmo @esmo_open @ASCO @AACRnews
#OncoTwitter #MedTwitter #LungCancer #NSCLC #Immunotherapy #ctDNA #PrecisionOncology #CancerResearch #ThoracicOncology
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Source: AACR 2026 现场信号 · x.com
