Ipilimumab 联合 Nivolumab、Encorafenib 联合 Binimetinib 治疗未经治突变型转移性黑色素瘤（SECOMBIT）：一项随机、三臂、开放标签的 II 期试验。
Sequencing of Ipilimumab Plus Nivolumab and Encorafenib Plus Binimetinib for Untreated -Mutated Metastatic Melanoma (SECOMBIT): A Randomized, Three-Arm, Open-Label Phase II Trial.
机构信息
Department of Melanoma, Cancer Immunotherapy and Development Therapeutics, I.N.T. IRCCS Fondazione "G. Pascale" Napoli, Naples, Italy.
Department of Oncology and Haematology, Papa Giovanni XXIII Cancer Center Hospital, Bergamo, Italy.
出版信息
J Clin Oncol. 2023 Jan 10;41(2):212-221. doi: 10.1200/JCO.21.02961. Epub 2022 Sep 1.
PURPOSE
Limited prospective data are available on sequential immunotherapy and BRAF/MEK inhibition for -mutant metastatic melanoma.
METHODS
SECOMBIT is a randomized, three-arm, noncomparative phase II trial (ClinicalTrials.gov identifier: NCT02631447). Patients with untreated, metastatic -mutant melanoma from 37 sites in nine countries were randomly assigned to arm A (encorafenib [450 mg orally once daily] plus binimetinib [45 mg orally twice daily] until progressive disease [PD] -> ipilimumab plus nivolumab [ipilimumab 3 mg/kg once every 3 weeks and nivolumab 1 mg/kg once every 3 weeks × four cycles -> nivolumab 3 mg/kg every 2 weeks]), arm B [ipilimumab plus nivolumab until PD -> encorafenib plus binimetinib], or arm C (encorafenib plus binimetinib for 8 weeks -> ipilimumab plus nivolumab until PD -> encorafenib plus binimetinib). The primary end point was overall survival (OS) at 2 years. Secondary end points included total progression-free survival, 3-year OS, best overall response rate, duration of response, and biomarkers in the intent-to-treat population. Safety was analyzed throughout sequential treatment in all participants who received at least one dose of study medication.
RESULTS
A total of 209 patients were randomly assigned (69 in arm A, 71 in arm B, and 69 in arm C). At a median follow-up of 32.2 (interquartile range, 27.9-41.6) months, median OS was not reached in any arm and more than 30 patients were alive in all arms. Assuming a null hypothesis of median OS of ≤ 15 months, the OS end point was met for all arms. The 2-year and 3-year OS rates were 65% (95% CI, 54 to 76) and 54% (95% CI, 41 to 67) in arm A, 73% (95% CI, 62 to 84) and 62% (95% CI, 48 to 76) in arm B, and 69% (95% CI, 59 to 80) and 60% (95% CI, 58 to 72) in arm C. No new safety signals emerged.
CONCLUSION
Sequential immunotherapy and targeted therapy provide clinically meaningful survival benefits for patients with -mutant melanoma.
目的
针对 - 突变型转移性黑色素瘤，有限的前瞻性数据可用于序贯免疫治疗和 BRAF/MEK 抑制。
方法
SECOMBIT 是一项随机、三臂、非对照的 II 期临床试验（ClinicalTrials.gov 标识符：NCT02631447）。来自 9 个国家 37 个地点未经治疗的转移性 - 突变型黑色素瘤患者被随机分配至 A 组（康奈非尼 [450 mg 口服，每日一次] 联合比美替尼 [45 mg 口服，每日两次]，直至疾病进展 [PD] -> 伊匹单抗联合纳武单抗 [伊匹单抗 3 mg/kg，每 3 周一次，纳武单抗 1 mg/kg，每 3 周一次 × 4 个周期 -> 纳武单抗 3 mg/kg，每 2 周一次]）、B 组（伊匹单抗联合纳武单抗直至 PD -> 康奈非尼联合比美替尼）或 C 组（康奈非尼联合比美替尼治疗 8 周 -> 伊匹单抗联合纳武单抗直至 PD -> 康奈非尼联合比美替尼）。主要终点为 2 年总生存率（OS）。次要终点包括总无进展生存期、3 年 OS、最佳总体缓解率、缓解持续时间和意向治疗人群中的生物标志物。对所有接受至少一剂研究药物的参与者，在整个序贯治疗中进行安全性分析。
结果
共有 209 名患者被随机分配（A 组 69 例，B 组 71 例，C 组 69 例）。在中位随访 32.2 个月（四分位距，27.9-41.6）时，任何组均未达到中位 OS，所有组均有超过 30 名患者存活。假设 OS 中位数≤15 个月的假设为零，所有组均达到 OS 终点。A 组 2 年和 3 年 OS 率分别为 65%（95%CI，54 至 76）和 54%（95%CI，41 至 67），B 组分别为 73%（95%CI，62 至 84）和 62%（95%CI，48 至 76），C 组分别为 69%（95%CI，59 至 80）和 60%（95%CI，58 至 72）。未出现新的安全性信号。
结论
序贯免疫治疗和靶向治疗为 - 突变型黑色素瘤患者提供了具有临床意义的生存获益。
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