阿维单抗联合洛拉替尼或克唑替尼治疗既往接受过治疗的晚期非小细胞肺癌患者：JAVELIN Lung 101试验的1b/2期结果

IF 3 Q2 ONCOLOGY JTO Clinical and Research Reports Pub Date : 2024-07-01 DOI:10.1016/j.jtocrr.2024.100685

Benjamin J. Solomon M.B.B.S., PhD , Ibiayi Dagogo-Jack MD , Se-Hoon Lee MD , Michael J. Boyer M.B.B.S., PhD , Suresh S. Ramalingam MD , Enric Carcereny MD , Enriqueta Felip MD, PhD , Ji-Youn Han MD, PhD , Toyoaki Hida PhD , Brett G.M. Hughes M.B.B.S. , Sang-We Kim MD, PhD , Makoto Nishio MD, PhD , Takashi Seto MD , Tatsuro Okamoto MD, PhD , Xiaoxi Zhang PhD , Jean-Francois Martini PhD , Erjian Wang MD, PhD , Steven De Beukelaer MD , Todd M. Bauer MD

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引用次数: 0

摘要

简介：JAVELIN Lung 101 1b/2 期试验评估了阿韦利单抗（免疫检查点抑制剂）与洛拉替尼或克唑替尼（酪氨酸激酶抑制剂）分别用于 ALK 阳性或 ALK 阴性晚期 NSCLC 的治疗效果。方法起始剂量为洛拉替尼 100 毫克，每天一次或克唑替尼 250 毫克，每天两次，每 2 周给予阿韦利单抗 10 毫克/千克。主要目标是评估第一阶段的最大耐受剂量（MTD）和第二阶段的推荐剂量，以及第二阶段的客观反应率。结果在阿维单抗加洛拉替尼组（ALK阳性；n = 31；1b期28例；2期3例），28例可评估患者中有2例（7%）出现DLT，MTD和2期推荐剂量为阿维单抗10 mg/kg，每2周1次，加洛拉替尼100 mg，每日1次。在阿韦鲁单抗加克唑替尼组（ALK阴性；n = 12；均为1b期）中，12名可评估患者中有5名（42%）出现了DLT，阿韦鲁单抗10毫克/千克，每2周一次，加克唑替尼250毫克，每天两次，超过了MTD；未评估其他克唑替尼剂量。阿维单抗加氯拉替尼的客观反应率为52%（95%置信区间，33%-70%）（完全反应，3%；部分反应，48%），阿维单抗加克唑替尼的客观反应率为25%（95%置信区间，6%-57%）（均为部分反应）。结论阿维单抗加氯拉替尼治疗ALK阳性NSCLC是可行的，但阿维单抗加克唑替尼治疗ALK阴性NSCLC在测试剂量下无法实施。两组均未观察到抗肿瘤活性增强的证据。

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Avelumab in Combination With Lorlatinib or Crizotinib in Patients With Previously Treated Advanced NSCLC: Phase 1b/2 Results From the JAVELIN Lung 101 Trial

Introduction

The JAVELIN Lung 101 phase 1b/2 trial evaluated avelumab (immune checkpoint inhibitor) combined with lorlatinib or crizotinib (tyrosine kinase inhibitors) in ALK-positive or ALK-negative advanced NSCLC, respectively.

Methods

Starting doses of lorlatinib 100 mg once daily or crizotinib 250 mg twice daily were administered with avelumab 10 mg/kg every 2 weeks. Primary objectives were assessment of maximum tolerated dose (MTD) and recommended phase 2 dose in phase 1 and objective response rate in phase 2. Primary end points were dose-limiting toxicity (DLT) and confirmed objective response per Response Evaluation Criteria in Solid Tumors, version 1.1.

Results

In the avelumab plus lorlatinib group (ALK-positive; n = 31; 28 in phase 1b; three in phase 2), two of 28 assessable patients (7%) had DLT, and the MTD and recommended phase 2 dose was avelumab 10 mg/kg every 2 weeks plus lorlatinib 100 mg once daily. In the avelumab plus crizotinib group (ALK-negative; n = 12; all phase 1b), five of 12 assessable patients (42%) had DLT, and the MTD was exceeded with avelumab 10 mg/kg every 2 weeks plus crizotinib 250 mg twice daily; alternative crizotinib doses were not assessed. Objective response rate was 52% (95% confidence interval, 33%–70%) with avelumab plus lorlatinib (complete response, 3%; partial response, 48%) and 25% (95% confidence interval, 6%–57%) with avelumab plus crizotinib (all partial responses).

Conclusions

Avelumab plus lorlatinib treatment in ALK-positive NSCLC was feasible, but avelumab plus crizotinib treatment in ALK-negative NSCLC could not be administered at the doses tested. No evidence of increased antitumor activity was observed in either group.