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

patients_and_methods

This open-label, phase III trial randomly assigned 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.

这项开放标签的III期试验随机将407名未接受治疗的晚期黑色素瘤患者以1:1的比例分配，接受皮下注射IO102-IO103（各85微克）加上每3周静脉注射200毫克的帕博利珠单抗，或仅接受帕博利珠单抗治疗，最长可达2年。

The primary endpoint was progression-free survival(PFS) by blinded independent central review per RECIST v1.1.

主要终点是根据RECIST v1.1标准，通过盲法独立中心审查的无进展生存期（PFS）。

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 6.0-14.8) for pembrolizumab [hazard ratio(HR) (95% CI) 0.77 (0.58-1.00), P = 0.0558]; the statistical significance threshold (P ≤ 0.045) was missed.

IO102-IO103联合派姆单抗的中位无进展生存期为19.4个月[95%置信区间（CI）9.7至未达到]，而单独使用派姆单抗的中位无进展生存期为11.0个月（95% CI 6.0-14.8）[风险比（HR）（95% CI）0.77（0.58-1.00），P = 0.0558]；未达到统计学显著性阈值（P ≤ 0.045）。

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 0.35-0.85)], anti-PD-1 naïve patients [24.8 versus 11.0 months (HR 0.74, 95% CI 0.56-0.98)], proto-oncogene B-Raf (BRAF)-mutated tumors, or elevated lactate dehydrogenase.

在大多数亚组中观察到联合治疗组的无进展生存期（PFS）更长，特别是在PD-L1阴性肿瘤患者中[中位PFS 16.6个月对比3.0个月（HR 0.54，95% CI 0.35-0.85）]，抗PD-1治疗未经验的患者[24.8个月对比11.0个月（HR 0.74，95% CI 0.56-0.98）]，原癌基因B-Raf（BRAF）突变肿瘤，或乳酸脱氢酶升高的患者。

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.

在疫苗组中，治疗相关不良事件3级或以上的频率没有增加（14.5%对比15.6%），严重不良事件的发生率也没有增加（32.0%对比32.3%）。

Local vaccine-related injection site reactions were reported in 56.0% of patients and were mostly grade 1/2.

56.0%的患者报告了与疫苗接种相关的局部注射部位反应，这些反应大多为1级/2级。

Conclusions

IO102-IO103 plus pembrolizumab prolonged PFS compared with pembrolizumab alone in patients with advanced melanoma in the first-line setting; however, statistical significance was missed for the primary endpoint.

在一线治疗晚期黑色素瘤患者中，IO102-IO103联合派姆单抗相较于单独使用派姆单抗，延长了无进展生存期（PFS）；然而，主要终点的统计学意义未达到。

The combination was well tolerated with no added significant systemic toxicity.

这种联合疗法耐受性良好，没有增加显著的全身性毒性。

These data show the potential benefit of this combination in untreated advanced melanoma.

这些数据展示了这种联合疗法在未治疗的晚期黑色素瘤中的潜在益处。