Vibostolimab Coformulated with Pembrolizumab Plus Chemotherapy as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer.

IF 5.1 3区医学 Q2 ONCOLOGY

Targeted Oncology Pub Date : 2026-10-20 DOI:10.1007/s11523-026-01237-w

Jacob Sands, Shun Lu, Joachim G Aerts, Martin Reck, Alejandro Navarro, Talia Shentzer Kutiel, Nir Peled, Ignacio Casarini, Samuel J Kerr, Toshiaki Takahashi, Ahmet Bilici, Ying Cheng, Mengzhao Wang, Shin Yup Lee, Anna Łowczak, Julien Mazieres, Haixia Hu, Jianyu Wu, Himani Aggarwal, Hazem El-Osta, Luis Paz-Ares

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引用次数: 0

Abstract

Background: Vibostolimab, an anti-T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT) antibody, showed antitumor activity with pembrolizumab in non-small-cell lung cancer.

Objective: The KEYVIBE-008 study evaluated vibostolimab coformulated with pembrolizumab (vibostolimab/pembrolizumab) plus etoposide and platinum-based chemotherapy (EP) versus atezolizumab plus EP as first-line therapy for extensive-stage small-cell lung cancer.

Methods: Participants aged ≥18 years with untreated extensive-stage small-cell lung cancer were randomized 1:1 to vibostolimab/pembrolizumab (200 mg each) or atezolizumab (1200 mg) every 3 weeks, with EP and cisplatin/carboplatin for the first four cycles. The primary endpoint was overall survival. The prespecified interim analysis included a non-binding futility analysis of overall survival (futility threshold for actual number of events, P = 0.4816).

Results: Four hundred and sixty participants were randomized (both arms, n = 230). Median time from randomization to data cutoff (4 June, 2024) was 16.6 (range 11.3‒26.1) months. The prespecified futility criterion for overall survival was met (hazard ratio 1.26; 95% confidence interval 1.00‒1.59; P = 0.9762). There was no difference in progression-free survival (hazard ratio 1.01; 95% confidence interval 0.82‒1.23) or objective response rates (71.7% with vibostolimab/pembrolizumab vs 74.8% with atezolizumab). Grade ≥3 treatment-related adverse events occurred in 66.8% of participants treated with vibostolimab/pembrolizumab and 57.2% treated with atezolizumab. Immune-mediated adverse events and infusion reactions occurred in 39.3% and 29.7% of participants, respectively.

Conclusions: In this interim analysis of vibostolimab/pembrolizumab plus EP versus atezolizumab plus EP as first-line therapy for extensive-stage small-cell lung cancer, the prespecified futility criterion for overall survival was met. Grade ≥3 treatment-related adverse events and immune-mediated adverse events were more frequent with vibostolimab/pembrolizumab versus atezolizumab. Given the overall benefit/risk profile, treatment with vibostolimab/pembrolizumab was discontinued.

Clinical trial registration: Clinicaltrials.gov, NCT05224141.

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Vibostolimab与Pembrolizumab联合化疗作为广泛期小细胞肺癌的一线治疗。

背景：Vibostolimab是一种具有免疫球蛋白和ITIM结构域（TIGIT）抗体的抗t细胞免疫受体，与派姆单抗在非小细胞肺癌中显示出抗肿瘤活性。目的：KEYVIBE-008研究评估了vibostolimab联合派姆单抗（vibostolimab/pembrolizumab）加依托泊苷和铂基化疗（EP）与阿特唑单抗加EP作为广泛期小细胞肺癌一线治疗的疗效。方法：年龄≥18岁的未经治疗的广泛期小细胞肺癌患者每3周按1:1随机分配到vibostolimab/pembrolizumab（各200 mg）或atezolizumab (1200 mg)，前4个周期使用EP和顺铂/卡铂。主要终点是总生存期。预先指定的中期分析包括总生存率的非约束性无效分析（实际事件数的无效阈值，P = 0.4816）。结果：460名参与者被随机化（两组，n = 230）。从随机分配到数据截止（2024年6月4日）的中位时间为16.6个月（11.3-26.1个月）。满足预先设定的总生存无效标准（风险比1.26；95%可信区间1.00-1.59;P = 0.9762）。无进展生存期（风险比1.01；95%可信区间0.82-1.23）或客观缓解率（vibostolimab/pembrolizumab组为71.7%，atezolizumab组为74.8%）无差异。66.8%的vibostolimab/pembrolizumab治疗组和57.2%的atezolizumab治疗组发生≥3级治疗相关不良事件。免疫介导的不良事件和输注反应分别发生在39.3%和29.7%的参与者中。结论：在vibostolimab/pembrolizumab + EP与atezolizumab + EP作为一线治疗广泛期小细胞肺癌的中期分析中，总生存期达到了预先设定的无效标准。vibostolimab/pembrolizumab与atezolizumab相比，治疗相关的≥3级不良事件和免疫介导的不良事件更频繁。考虑到总体获益/风险情况，停止使用vibostolimab/pembrolizumab治疗。临床试验注册：Clinicaltrials.gov, NCT05224141。

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来源期刊

Targeted Oncology 医学-肿瘤学

CiteScore

8.40

自引率

3.70%

发文量

审稿时长

>12 weeks

期刊介绍： Targeted Oncology addresses physicians and scientists committed to oncology and cancer research by providing a programme of articles on molecularly targeted pharmacotherapy in oncology. The journal includes: Original Research Articles on all aspects of molecularly targeted agents for the treatment of cancer, including immune checkpoint inhibitors and related approaches. Comprehensive narrative Review Articles and shorter Leading Articles discussing relevant clinically established as well as emerging agents and pathways. Current Opinion articles that place interesting areas in perspective. Therapy in Practice articles that provide a guide to the optimum management of a condition and highlight practical, clinically relevant considerations and recommendations. Systematic Reviews that use explicit, systematic methods as outlined by the PRISMA statement. Adis Drug Reviews of the properties and place in therapy of both newer and established targeted drugs in oncology.