这是一项巴伐利亚北欧 (BN)-Brachyury 疫苗加放疗 (RT) 的单组 2 期临床试验，旨在确定该组合的客观缓解率 (ORR)、无进展生存期 (PFS) 和安全性。总共 29 名晚期脊索瘤成年患者在 RT 前接受了两剂改良痘苗安卡拉-巴伐利亚北欧 (MVA-BN)-Brachyury 皮下初免疫苗和一剂鸡痘病毒 (FPV)-Brachyury 疫苗治疗。 RT 后，每 4 周注射 4 剂 FPV-Brachyury 加强疫苗，然后每 12 周（第 110 周）注射一次。每个靶标的一次分次的最小 RT 剂量要求 >8 Gy。通过修改后的实体瘤疗效评估标准 1.1 (mRECIST) 评估疗效，其中仅将放射病灶视为靶标，并通过标准 RECIST 1.1 在一部分患者中进行评估。26 名可评估患者中，有 2 名经历了持久部分缓解 (PR)（ORR 为7.7%；90% 置信区间 [CI]，2.6-20.8]）根据 mRECIST 1.1。根据 mRECIST 1.1 的最佳缓解，共有 21 名患者（80.8%；90% CI，65.4-90.3）疾病稳定，3 名患者（11.5%；90% CI，4.7-25.6）疾病进展。研究期间未达到中位 PFS。该试验证实了 BN-Brachyury 和 RT 的安全性。尽管该研究没有达到 29 名患者出现 4 次缓解的预定研究目标，但我们确实观察到 2 例 PR 和 2 年以上的 PFS。对于脊索瘤（一种反应率较低的极其罕见的疾病）的基于疫苗的研究，可能需要进行随机研究或新颖的试验设计来确认活性。© 2024 美国癌症协会。

This was a single-arm, phase 2 clinical trial of Bavarian Nordic (BN)-Brachyury vaccine plus radiotherapy (RT) designed to determine the objective response rate (ORR), progression-free survival (PFS), and safety of the combination in chordoma.A total of 29 adult patients with advanced chordoma were treated with two subcutaneous priming vaccine doses of modified vaccinia Ankara-Bavarian Nordic (MVA-BN)-Brachyury and one vaccine dose of fowlpox virus (FPV)-Brachyury before RT. After RT, booster vaccinations were given with FPV-Brachyury every 4 weeks for 4 doses, then every 12 weeks (week 110). A minimum RT dose of >8 Gy in one fraction for each target was required. Response was evaluated by modified Response Evaluation Criteria in Solid Tumors 1.1 (mRECIST), where only radiated lesions were considered targets, and by standard RECIST 1.1 in a subset of patients.Two of 26 evaluable patients experienced durable partial response (PR) (ORR of 7.7%; 90% confidence interval [CI], 2.6-20.8]) by mRECIST 1.1. A total of 21 patients (80.8%; 90% CI, 65.4-90.3) had stable disease, and three patients (11.5%; 90% CI, 4.7-25.6) had progressive disease as best response per mRECIST 1.1. Median PFS was not reached during the study.This trial confirms the safety of BN-Brachyury and RT. Although the study did not meet the predefined study goal of four responses in 29 patients, we did observe two PRs and a PFS of greater than 2 years. For a vaccine-based study in chordoma, an ultra-rare disease where response rates are low, a randomized study or novel trial designs may be required to confirm activity.© 2024 American Cancer Society.