纳武利尤单抗和雷莫芦单抗治疗抗程序性死亡-1/程序性死亡配体 1 治疗后进展的晚期黑色素瘤患者：RELATIVITY-020 试验的 I/IIa 期结果。
Nivolumab and Relatlimab in Patients With Advanced Melanoma That Had Progressed on Anti-Programmed Death-1/Programmed Death Ligand 1 Therapy: Results From the Phase I/IIa RELATIVITY-020 Trial.
机构信息
Melanoma, Cancer Immunotherapy, and Development Therapeutics Unit, Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale," Naples, Italy.
Sidney Kimmel Comprehensive Cancer Center, Bloomberg-Kimmel Institute for Cancer Immunotherapy, Johns Hopkins University School of Medicine, Baltimore, MD.
出版信息
J Clin Oncol. 2023 May 20;41(15):2724-2735. doi: 10.1200/JCO.22.02072. Epub 2023 Feb 13.
PURPOSE
Nivolumab and relatlimab activity in advanced melanoma with prior progression on anti-programmed death-1/programmed death ligand 1 (PD-(L)1)-containing regimens is under investigation. RELATIVITY-047 demonstrated significantly improved progression-free survival (PFS) for nivolumab and relatlimab over nivolumab in previously untreated advanced melanoma.
METHODS
The phase I/IIa, open-label RELATIVITY-020 trial part D assessed efficacy and safety of nivolumab and relatlimab in advanced melanoma with progression during, or within 3 months of, 1 (D1) or ≥ 1 (D2) anti-PD-(L)1-containing regimens. Safety was a primary end point. Objective response rate (coprimary end point) and PFS by blinded independent central review (BICR) were assessed.
RESULTS
Five hundred eighteen patients (D1 = 354; D2 = 164) received nivolumab and relatlimab. Among evaluable patients, the objective response rate by BICR was 12.0% (95% CI, 8.8 to 15.8) in D1 (n = 351) and 9.2% (95% CI, 5.2 to 14.7) in D2 (n = 163). Responses appeared to be enriched among patients with tumors expressing programmed death ligand 1 or lymphocyte activation gene 3; however, responses were observed regardless of programmed death ligand 1 and lymphocyte activation gene 3 expression (1%). The median duration of response was not reached (95% CI, 12.9 to not reached) in D1 and 12.8 months (95% CI, 6.9 to 12.9) in D2. The median PFS by BICR was 2.1 months (95% CI, 1.9 to 3.5) in D1 and 3.2 months (95% CI, 1.9 to 3.6) in D2; the 6-month PFS rate was 29.1% (95% CI, 24.2 to 34.1) and 27.7% (95% CI, 20.5 to 35.4), respectively. The grade 3-4 treatment-related adverse event incidence was 15.0% in D1 and 12.8% in D2. One case of grade 3 myocarditis and no treatment-related deaths occurred across part D.
CONCLUSION
Nivolumab and relatlimab had a manageable safety profile and demonstrated durable clinical activity in a proportion of patients with heavily pretreated advanced melanoma with prior progression on anti-PD-(L)1-containing regimens.
UNLABELLED
[Media: see text].
目的
在先前接受过含程序性死亡受体-1/程序性死亡配体 1（PD-（L）1）方案治疗的晚期黑色素瘤患者中，纳武利尤单抗和雷利利单抗在抗程序性死亡受体-1/程序性死亡配体 1（PD-（L）1）方案治疗期间或之后 3 个月内进展的患者中的活性正在研究中。RELATIVITY-047 显示纳武利尤单抗和雷利利单抗与纳武利尤单抗相比，在未经治疗的晚期黑色素瘤患者中显著改善了无进展生存期（PFS）。
方法
在开放标签的 I/IIa 期 RELATIVITY-020 试验的 D 部分，评估了纳武利尤单抗和雷利利单抗在先前接受过 1（D1）或≥1（D2）种含 PD-（L）1 方案治疗期间或之后进展的晚期黑色素瘤患者中的疗效和安全性。安全性是主要终点。通过盲法独立中心评估（BICR）评估客观缓解率（共同主要终点）和 PFS。
结果
518 例患者（D1 = 354 例；D2 = 164 例）接受了纳武利尤单抗和雷利利单抗治疗。在可评估的患者中，BICR 评估的客观缓解率在 D1（n = 351）中为 12.0%（95%CI，8.8 至 15.8），在 D2（n = 163）中为 9.2%（95%CI，5.2 至 14.7）。在肿瘤表达程序性死亡配体 1 或淋巴细胞激活基因 3 的患者中，缓解似乎更为丰富；然而，无论程序性死亡配体 1 和淋巴细胞激活基因 3 的表达情况如何（1%），均观察到缓解。D1 中未达到缓解的中位持续时间（95%CI，12.9 至无法评估）和 D2 中为 12.8 个月（95%CI，6.9 至 12.9）。BICR 评估的中位 PFS 在 D1 中为 2.1 个月（95%CI，1.9 至 3.5），在 D2 中为 3.2 个月（95%CI，1.9 至 3.6）；6 个月的 PFS 率分别为 29.1%（95%CI，24.2 至 34.1）和 27.7%（95%CI，20.5 至 35.4）。D1 中 3-4 级治疗相关不良事件发生率为 15.0%，D2 中为 12.8%。在 D 部分中，发生了 1 例 3 级心肌炎和 1 例与治疗相关的死亡病例。
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