Vo Henry Hiep, Cartwright Carrie, Song I-Wen, Karp Daniel D, Nogueras Gonzalez Graciela M, Xie Yuran, Karol Michael, Hitron Matthew, Vining David, Tsimberidou Apostolia-Maria
Department of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030, USA.
Cancers (Basel). 2022 Mar 4;14(5):1330. doi: 10.3390/cancers14051330.
: BBI608 is an investigational reactive oxygen species generator that affects several molecular pathways. We investigated BBI608 combined with immune checkpoint inhibitors in patients with advanced cancers. : BBI608 (orally twice daily) was combined with ipilimumab (3 mg/kg IV every 3 weeks); pembrolizumab (2 mg/kg IV every 3 weeks); or nivolumab (3 mg/kg IV every 4 weeks). We assessed the safety, antitumor activity and the pharmacokinetic profile of BBI combined with immunotherapy. From 1/2017 to 3/2017, 12 patients were treated (median age, 54 years; range, 31-78; 6 men). Treatment was overall well tolerated. No dose-limiting toxicity was observed. The most common adverse events were diarrhea (5 patients: grade (G)1-2, = 3; G3, = 2) and nausea (4 patients, all G1). Prolonged disease stabilization was noted in five patients treated with BBI608/nivolumab lasting for 12.1, 10.1, 8.0, 7.7 and 7.4 months. The median progression-free survival was 2.73 months. The median overall survival was 7.56 months. Four patients had prolonged overall survival (53.0, 48.7, 51.9 and 48.2 months). : Checkpoint inhibitors combined with BBI608 were well tolerated. Several patients had prolonged disease stabilization and overall survival. Prospective studies to elucidate the mechanisms of response and resistance to BBI608 are warranted.
BBI608是一种影响多种分子途径的研究性活性氧生成剂。我们研究了BBI608与免疫检查点抑制剂联合用于晚期癌症患者的情况。BBI608（每日口服两次）与伊匹单抗（每3周静脉注射3mg/kg）、帕博利珠单抗（每3周静脉注射2mg/kg）或纳武单抗（每4周静脉注射3mg/kg）联合使用。我们评估了BBI与免疫疗法联合使用时的安全性、抗肿瘤活性和药代动力学特征。2017年1月至2017年3月，对12例患者进行了治疗（中位年龄54岁；范围31 - 78岁；男性6例）。治疗总体耐受性良好。未观察到剂量限制性毒性。最常见的不良事件是腹泻（5例患者：1 - 2级，n = 3；3级，n = 2）和恶心（4例患者，均为1级）。在接受BBI608/纳武单抗治疗的5例患者中观察到疾病长期稳定，持续时间分别为12.1、10.1、8.0、7.7和7.4个月。中位无进展生存期为2.73个月。中位总生存期为7.56个月。4例患者总生存期延长（53.0、48.7、51.9和48.2个月）。免疫检查点抑制剂与BBI608联合使用耐受性良好。数例患者疾病长期稳定且总生存期延长。有必要进行前瞻性研究以阐明对BBI608的反应和耐药机制。
