Suppr
超能文献

纳武利尤单抗联合瑞派利单抗及纳武利尤单抗联合伊匹木单抗治疗晚期肾细胞癌患者：开放标签、随机、II期FRACTION-RCC试验结果

Nivolumab plus relatlimab and nivolumab plus ipilimumab for patients with advanced renal cell carcinoma: results from the open-label, randomised, phase II FRACTION-RCC trial.

作者信息

Choueiri T K, Kuzel T M, Tykodi S S, Verzoni E, Kluger H, Nair S, Perets R, George S, Gurney H, Pachynski R K, Folefac E, Castonguay V, Lee C-H, Vaishampayan U, Miller W H, Bhagavatheeswaran P, Wang Y, Gupta S, DeSilva H, Lee C-W, Escudier B, Motzer R J

机构信息

Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute, Boston, MA, USA; Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Division of Hematology/Oncology/Cell Therapy, Rush University Medical Center, Chicago, IL, USA.

出版信息

ESMO Open. 2024 Dec;9(12):104073. doi: 10.1016/j.esmoop.2024.104073. Epub 2024 Dec 5.

DOI:10.1016/j.esmoop.2024.104073

PMID:39642635

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11667034/

Abstract

BACKGROUND

The Fast Real-time Assessment of Combination Therapies in Immuno-ONcology study in patients with aRCC (FRACTION-RCC) was designed to assess new immuno-oncology (IO) combinations in patients with advanced renal cell carcinoma (aRCC). We present results in IO-naive patients treated with nivolumab (NIVO) + relatlimab (RELA) or NIVO + ipilimumab (IPI) in track 1.

METHODS

The open-label, randomised, phase II FRACTION-RCC trial enrolled patients with aRCC from 32 hospitals and cancer centres across six countries. Patients were enrolled in track 1 (IO-naive) or track 2 (IO-experienced). IO-naive patients were stratified by previous tyrosine kinase inhibitor therapy and randomised to NIVO (240 mg) + RELA (80 mg) intravenously once every 2 weeks or NIVO (3 mg/kg) + IPI (1 mg/kg) intravenously once every 3 weeks for four doses, followed by NIVO (480 mg) once every 4 weeks, each up to ∼2 years. The primary endpoints were objective response by investigator (RECIST version 1.1), duration of response (DOR), and progression-free survival (PFS) rate at 24 weeks. Safety was a secondary endpoint; biomarker analyses were exploratory.

RESULTS

FRACTION-RCC enrolled patients between 2 February 2017 and 23 January 2020. In track 1, 30 patients each were treated with NIVO + RELA or NIVO + IPI (clinical database lock, 1 November 2021). With NIVO + RELA [median follow-up, 48.6 months; interquartile range (IQR) 46.9-51.7 months], objective response was 30% [95% confidence interval (CI) 15% to 49%], with 33 weeks (95% CI 16-53 weeks) median DOR. The PFS rate at 24 weeks was 43% (95% CI 25% to 60%). With NIVO + IPI (median follow-up, 48.7 months; IQR 47.1-52.0 months), the objective response was 20% (95% CI 8% to 39%), with the median DOR not reached (95% CI 33 weeks-not estimable). The PFS rate at 24 weeks was 49% (95% CI 29% to 66%). Higher baseline lymphocyte activation gene 3 (LAG-3) and programmed death-ligand 1 (PD-L1) expression levels were detected among track 1 NIVO + RELA responders. Grade 3-4 treatment-related adverse events were reported in 4/30 (13%) patients treated with NIVO + RELA and 10/30 (33%) patients treated with NIVO + IPI. No deaths were attributed to study treatments.

CONCLUSIONS

Results showed antitumour activity and manageable safety with NIVO + RELA. Findings also support NIVO + IPI as an effective combination regimen in IO-naive patients with aRCC.

摘要

背景

晚期肾细胞癌（aRCC）患者免疫肿瘤联合疗法快速实时评估研究（FRACTION - RCC）旨在评估晚期肾细胞癌患者的新型免疫肿瘤（IO）联合疗法。我们展示了在第1组中接受纳武利尤单抗（NIVO）+瑞派利单抗（RELA）或NIVO + 伊匹木单抗（IPI）治疗的初治IO患者的结果。

方法

开放标签、随机、II期FRACTION - RCC试验纳入了来自六个国家32家医院和癌症中心的aRCC患者。患者被纳入第1组（初治IO）或第2组（经治IO）。初治IO患者根据既往酪氨酸激酶抑制剂治疗情况进行分层，随机分为每2周静脉注射一次NIVO（240 mg）+ RELA（80 mg）或每3周静脉注射一次NIVO（3 mg/kg）+ IPI（1 mg/kg），共注射四剂，随后每4周注射一次NIVO（480 mg），每种方案最长持续约2年。主要终点为研究者评估的客观缓解率（根据RECIST 1.1版标准）、缓解持续时间（DOR）以及24周时的无进展生存率（PFS）。安全性为次要终点；生物标志物分析为探索性研究。

结果

FRACTION - RCC在2017年2月2日至2020年1月23日期间纳入患者。在第1组中，各有30例患者接受NIVO + RELA或NIVO + IPI治疗（临床数据库锁定时间为2021年11月1日）。接受NIVO + RELA治疗的患者（中位随访时间48.6个月；四分位间距[IQR] 46.9 - 51.7个月），客观缓解率为30%[95%置信区间（CI）15%至49%]，中位DOR为33周（95% CI 16 - 53周）。24周时的PFS率为43%（95% CI 25%至60%）。接受NIVO + IPI治疗的患者（中位随访时间48.7个月；IQR 47.1 - 52.0个月），客观缓解率为20%（95% CI 8%至39%），中位DOR未达到（95% CI 33周 - 无法估计）。24周时的PFS率为49%（95% CI 29%至66%）。在第1组接受NIVO + RELA治疗的缓解者中检测到更高的基线淋巴细胞激活基因3（LAG - 3）和程序性死亡配体1（PD - L1）表达水平。接受NIVO + RELA治疗的4/30（13%）患者和接受NIVO + IPI治疗的10/30（33%）患者报告了3 - 4级治疗相关不良事件。没有死亡病例归因于研究治疗。