IO102-IO103 immune-modulatory cancer vaccine and pembrolizumab in melanoma.

IF 65.4 1区医学 Q1 ONCOLOGY

Annals of Oncology Pub Date : 2026-04-21 DOI:10.1016/j.annonc.2026.04.010

J C Hassel, A Arance, M S Carlino, L Mortier, P A Ascierto, P Rutkowski, S Sandhu, C Coetzee, I Puzanov, S B Karaca, A M Eggermont, O Hamid, S Grabbe, A Poklepovic, T Amaral, D Schadendorf, B Schilling, A Vedel Christiansen, B Wang, A Wakatsuki Pedersen, Q Ahmad, M B Zocca, F Ringeisen, C Robert, I M Svane

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引用次数: 0

Abstract

Background: IO102-IO103, an investigational, immune-modulatory cancer vaccine, targets both tumor cells and immune-suppressive cells within the tumor microenvironment through activation and expansion of T cells against indoleamine 2,3-dioxygenase 1(IDO1)-positive and/or programmed death ligand 1 (PD-L1)-positive cells.

Patients and methods: This open-label, Phase 3 trial randomized 407 patients with untreated advanced melanoma in a 1:1 ratio to receive subcutaneous IO102-IO103 (85 μg each) plus pembrolizumab 200 mg intravenously every 3 weeks or pembrolizumab alone for up to 2 years. The primary endpoint was progression-free survival (PFS) by blinded independent central review per RECIST v1.1.

Results: The median PFS was 19.4 months (95% confidence interval [CI], 9.7 to not reached) for IO102-IO103 plus pembrolizumab versus 11.0 months (95% CI, 6.0 to 14.8) for pembrolizumab (hazard ratio [HR] [95% CI], 0.77 [0.58 to 1.00]; P = 0.0558); the statistical significance threshold (P ≤ 0.045) was missed. A longer PFS was observed in the combination arm across most subgroups, notably in patients with PD-L1-negative tumors (median PFS 16.6 versus 3.0 months [HR, 0.54; 95% CI, 0.35 to 0.85]), anti-PD-1 naïve patients (24.8 versus 11.0 months [HR, 0.74; 95% CI, 0.56 to 0.98]), proto-oncogene B-Raf (BRAF) mutated tumors, or elevated lactate dehydrogenase. There was no increase in the frequency of treatment-related adverse events grade ≥3 (14.5% versus 15.6%) or of serious adverse events (32.0% versus 32.3%) in the vaccine arm. Local vaccine-related injection site reactions were reported in 56.0% of patients and were mostly grade 1/2.

Conclusions: IO102-IO103 plus pembrolizumab prolonged progression-free survival compared with pembrolizumab alone in patients with advanced melanoma in the first-line setting; however, statistical significance was missed for the primary endpoint. The combination was well tolerated with no added significant systemic toxicity. These data show the potential benefit of this combination in untreated advanced melanoma.

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IO102-IO103免疫调节性癌症疫苗和派姆单抗在黑色素瘤中的应用。

背景：IO102-IO103是一种正在研究的免疫调节性癌症疫苗，通过激活和扩增T细胞来靶向肿瘤细胞和肿瘤微环境中的免疫抑制细胞，以对抗吲哚胺2,3-双加氧酶1（IDO1）阳性和/或程序性死亡配体1（PD-L1）阳性细胞。患者和方法：这项开放标签的3期试验以1:1的比例随机分配407例未经治疗的晚期黑色素瘤患者，接受皮下IO102-IO103（每个85 μg）加派姆单抗200 mg静脉注射，每3周或单独使用派姆单抗长达2年。主要终点是根据RECIST v1.1进行的盲法独立中心评价的无进展生存期（PFS）。结果：IO102-IO103联合派姆单抗的中位PFS为19.4个月（95%可信区间[CI]， 9.7至未达到），而派姆单抗的中位PFS为11.0个月（95% CI， 6.0至14.8）（风险比[HR] [95% CI]， 0.77[0.58至1.00];P = 0.0558）；未达统计学显著性阈值（P≤0.045）。在大多数亚组中，联合治疗组观察到更长的PFS，特别是pd - l1阴性肿瘤患者（中位PFS为16.6个月vs . 3.0个月[HR， 0.54; 95% CI， 0.35至0.85]）、抗pd -1 naïve患者（24.8个月vs . 11.0个月[HR， 0.74; 95% CI， 0.56至0.98]）、原癌基因B-Raf （BRAF）突变肿瘤或乳酸脱氢酶升高。在疫苗组中，治疗相关不良事件≥3级（14.5%对15.6%）或严重不良事件（32.0%对32.3%）的频率没有增加。56.0%的患者报告了局部疫苗相关注射部位反应，大多数为1/2级。结论：在一线治疗的晚期黑色素瘤患者中，与单独使用派姆单抗相比，IO102-IO103联合派姆单抗延长了无进展生存期；然而，主要终点没有统计学意义。联合用药耐受性良好，没有增加明显的全身毒性。这些数据表明，在未经治疗的晚期黑色素瘤中，这种联合疗法有潜在的益处。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Annals of Oncology 医学-肿瘤学

CiteScore

63.90

自引率

1.00%

发文量

3712

审稿时长

2-3 weeks

期刊介绍： Annals of Oncology, the official journal of the European Society for Medical Oncology and the Japanese Society of Medical Oncology, offers rapid and efficient peer-reviewed publications on innovative cancer treatments and translational research in oncology and precision medicine. The journal primarily focuses on areas such as systemic anticancer therapy, with a specific emphasis on molecular targeted agents and new immune therapies. We also welcome randomized trials, including negative results, as well as top-level guidelines. Additionally, we encourage submissions in emerging fields that are crucial to personalized medicine, such as molecular pathology, bioinformatics, modern statistics, and biotechnologies. Manuscripts related to radiotherapy, surgery, and pediatrics will be considered if they demonstrate a clear interaction with any of the aforementioned fields or if they present groundbreaking findings. Our international editorial board comprises renowned experts who are leaders in their respective fields. Through Annals of Oncology, we strive to provide the most effective communication on the dynamic and ever-evolving global oncology landscape.