MRTX-500二期试验：Sitravatinib联合Nivolumab治疗在检查点抑制剂治疗或化疗中后进展非鳞非小细胞肺癌患者

SCI

17 March 2023

MRTX-500 Phase 2 Trial: Sitravatinib With Nivolumab in Patients With NonSquamous Non-Small Cell Lung Cancer Progressing On/After Checkpoint Inhibitor Therapy or Chemotherapy

 (JTO, IF: 20.121)

He Kai,Berz David,Gadgeel Shirish M et al. MRTX-500 Phase 2 Trial: Sitravatinib With Nivolumab in Patients With Non-Squamous Non-Small Cell Lung Cancer Progressing On/After Checkpoint Inhibitor Therapy or Chemotherapy.[J] .J Thorac Oncol, 2023, undefined: undefined.

INTRODUCTION 介绍

Sitravatinib, a receptor tyrosine kinase inhibitor targeting TAM receptors and VEGFR2, can shift the tumor microenvironment towards an immunostimulatory state. Combining sitravatinib with checkpoint inhibitors (CPI) may augment antitumor activity.

Sitravatinib是一种受体酪氨酸激酶抑制剂，靶点为TAM受体和VEGFR2，可以将肿瘤微环境转变为免疫刺激状态。Sitravatinib联合检查点抑制剂(CPI)可增强抗肿瘤活性。

METHODS 方法

The phase 2 MRTX-500 study evaluated sitravatinib (120 mg daily) with nivolumab (every 2/4 weeks) in patients with advanced non-squamous non-small cell lung cancer (NSCLC) who progressed on/after prior CPI (CPI-experienced) or chemotherapy (CPI-naïve). CPI-experienced patients had prior clinical benefit (PCB; complete/partial response or stable disease for ≥12 weeks then disease progression) or no PCB (NPCB) from CPI. Primary endpoint was objective response rate (ORR); secondary objectives included safety and secondary efficacy endpoints.

2期MRTX-500研究评估了Sitravatinib(120mg/d)联合Nivolumab(每2/4周)治疗在既往CPI或无CPI化疗期间/之后进展的晚期非鳞非小细胞肺癌(NSCLC)患者。CPI患者有先前的临床获益(PCB;完全/部分缓解或疾病稳定≥12周后疾病进展)或无PCB (NPCB)。主要终点为客观有效率(ORR);次要目标包括安全性和次要疗效终点。

RESULTS 结果  

Overall, 124 CPI-experienced (NPCB, n = 35; PCB, n = 89) and 32 CPI-naïve patients were treated. Investigator-assessed ORR was 11.4% in patients with NPCB, 16.9% with PCB, and 25.0% in CPI-naïve. Median progression-free survival was 3.7, 5.6, and 7.1 months with NPCB, PCB, and CPI-naïve, respectively; median overall survival was 7.9 and 13.6 months with NPCB and PCB, respectively (not reached in CPI-naïve patients; median follow-up 20.4 months). Overall, (N = 156), any grade treatment-related adverse events (TRAEs) occurred in 93.6%; grade 3/4 in 58.3%. One grade 5 TRAE occurred in a CPI-naïve patient. TRAEs led to treatment discontinuation in 14.1% and dose reduction/interruption in 42.9%. Biomarker analyses supported an immunostimulatory mechanism of action.

总体而言，124例CPI患者(NPCB, n = 35;PCB, n = 89)和32例无CPI患者接受治疗。研究人员评估的ORR在NPCB患者中为11.4%，PCB患者为16.9%，无CPI患者为25.0%。NPCB、PCB和无CPI患者的中位无进展生存期分别为3.7、5.6和7.1个月;NPCB和PCB患者的中位总生存期分别为7.9和13.6个月(无CPI患者未达到;中位随访20.4个月)。总体而言(N = 156)，发生任何级别治疗相关不良事件(TRAEs)的比例为93.6%；3/4级占58.3%。无CPI患者发生1例5级TRAE。TRAEs导致14.1%的治疗中断，42.9%的剂量减少/中断。生物标志物分析支持免疫刺激作用机制。

CONCLUSIONS 结论  

Sitravatinib with nivolumab had a manageable safety profile. Although ORR was not met, this combination demonstrated antitumor activity and encouraging survival in CPI-experienced patients with non-squamous NSCLC.

Sitravatinib联合Nivolumab具有可控的安全性。尽管ORR未达到，但该联合疗法显示出抗肿瘤活性，并提高了有CPI的非鳞NSCLC患者的生存。

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