Phase Ib study of patients with metastatic castrate-resistant prostate cancer treated with different sequencing regimens of atezolizumab and sipuleucel-T.
Phase Ib study of patients with metastatic castrate-resistant prostate cancer treated with different sequencing regimens of atezolizumab and sipuleucel-T.
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DOI：
10.1136/jitc-2021-002931
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发表时间：
2021-08
影响因子：
10.9
通讯作者：
Rosser C
中科院分区：
文献类型：
--
作者：
Dorff T;Hirasawa Y;Acoba J;Pagano I;Tamura D;Pal S;Zhang M;Waitz R;Dhal A;Haynes W;Shon J;Scholz M;Furuya H;Chan OTM;Huang J;Rosser C
将免疫检查点抑制剂与肿瘤疫苗相结合，可能会调节免疫系统，以利用互补的作用机制，导致转移性去势耐受前列腺癌(MCRPC)持续的T细胞激活和有效的长期免疫治疗反应。无症状或无症状的mCRPC受试者按1：1的比例随机分配，接受阿特唑珠单抗后再接受siPuleucel-T(组1)或siPuleucel-T再接受阿替唑单抗(组2)。主要终点是安全性，而次要终点包括初步的临床活动，如客观的肿瘤反应和全身免疫反应，这些反应可以确定与序贯使用阿替唑单抗和西普利-T相关的关键分子和免疫学变化。共有37名受试者入选。受试者年龄中位数为75.0岁，前列腺特异性抗原(PSA)中位数为2 1.9 ng/m L，治疗前中位数为3次。大多数受试者(83.8%)至少有一次与治疗相关的不良事件。没有任何一种研究药物的4级或5级毒性。免疫相关不良事件和输液反应发生率为13.5%，均为1~2级。23例符合实体瘤可测疾病疗效评价标准的受试者中，6个月时仅有1例患者部分缓解(PR)，4例患者病情稳定(SD)，客观缓解率为4.3%，疾病控制率为21.7%。T细胞受体多样性在有反应的受试者中更高，包括SD。对三种新抗原(SIK3、KDM1A/LSD1和PIK3R6)的免疫应答随着治疗的进行而增强。总体而言，无论给药顺序如何，阿替唑单抗与西普利-T联合使用似乎是安全的，耐受性良好，其安全性与作为单一治疗的每种药物相当。相关的免疫研究可能表明这种结合是有益的；然而，还需要进一步的研究。NCT03024216。
Combining an immune checkpoint inhibitor with a tumor vaccine may modulate the immune system to leverage complementary mechanisms of action that lead to sustained T-cell activation and a potent prolonged immunotherapeutic response in metastatic castration resistant prostate cancer (mCRPC). Subjects with asymptomatic or minimally symptomatic mCRPC were randomly assigned in a 1:1 ratio to receive either atezolizumab followed by sipuleucel-T (Arm 1) or sipuleucel-T followed by atezolizumab (Arm 2). The primary endpoint was safety, while secondary endpoints included preliminary clinical activity such as objective tumor response and systemic immune responses that could identify key molecular and immunological changes associated with sequential administration of atezolizumab and sipuleucel-T. A total of 37 subjects were enrolled. The median age was 75.0 years, median prostate specific antigen (PSA) was 21.9 ng/mL, and subjects had a median number of three prior treatments. Most subjects (83.8%) had at least one treatment-related adverse event. There were no grade 4 or 5 toxicities attributed to either study drug. Immune-related adverse events and infusion reactions occurred in 13.5% of subjects, and all of which were grade 1 or 2. Of 23 subjects with Response Evaluation Criteria in Solid Tumors measurable disease, only one subject in Arm 2 had a partial response (PR) and four subjects overall had stable disease (SD) at 6 months reflecting an objective response rate of 4.3% and a disease control rate of 21.7%. T-cell receptor diversity was higher in subjects with a response, including SD. Immune response to three novel putative antigens (SIK3, KDM1A/LSD1, and PIK3R6) appeared to increase with treatment. Overall, regardless of the order in which they were administered, the combination of atezolizumab with sipuleucel-T appears to be safe and well tolerated with a comparable safety profile to each agent administered as monotherapy. Correlative immune studies may suggest the combination to be beneficial; however, further studies are needed. NCT03024216.
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DOI：
10.1073/pnas.1808790115
发表时间：
2018-11-13
影响因子：
11.1
作者：
Bausch-Fluck D;Goldmann U;Müller S;van Oostrum M;Müller M;Schubert OT;Wollscheid B
通讯作者：
Wollscheid B
影响因子：
14.9
作者：
Almeida LG;Sakabe NJ;deOliveira AR;Silva MC;Mundstein AS;Cohen T;Chen YT;Chua R;Gurung S;Gnjatic S;Jungbluth AA;Caballero OL;Bairoch A;Kiesler E;White SL;Simpson AJ;Old LJ;Camargo AA;Vasconcelos AT
通讯作者：
Vasconcelos AT
影响因子：
158.5
作者：
Parker, C.;Nilsson, S.;Sartor, O.
通讯作者：
Sartor, O.
影响因子：
158.5
作者：
Kantoff, Philip W.;Higano, Celestia S.;Young, J.
通讯作者：
Young, J.
具有转移性cast割前列腺癌的男性的鲁卡巴里（Rucaparib）具有BRCA1或BRCA2基因改变。
DOI：
10.1200/jco.20.01035
发表时间：
2020-11-10
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Abida W;Patnaik A;Campbell D;Shapiro J;Bryce AH;McDermott R;Sautois B;Vogelzang NJ;Bambury RM;Voog E;Zhang J;Piulats JM;Ryan CJ;Merseburger AS;Daugaard G;Heidenreich A;Fizazi K;Higano CS;Krieger LE;Sternberg CN;Watkins SP;Despain D;Simmons AD;Loehr A;Dowson M;Golsorkhi T;Chowdhury S;TRITON2 investigators
通讯作者：
TRITON2 investigators