A Phase II Study of N-803 Alone or in Combination With BN-Brachyury Vaccine or Bintrafusp Alfa (M7824) for Participants With Castration Resistant Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Clinical Efficacy of N-803 alone or in combination with brachyury vaccine or bintrafusp alfa
研究概览
简要总结
Background:
Prostate cancer does not trigger a strong immune response in the body. Hormone therapy, to reduce levels of testosterone in the body, can be helpful to treat some prostate cancers. However, castration-resistant prostate cancer (CRPC) keeps growing even when the testosterone is reduced to a very low level. Men with metastatic CRPC survive an average of only 3 years. More effective treatments are needed.
Objective:
To test whether an immunotherapy drug (N-803), alone or in combination with other drugs, can help treat CRPC.
Eligibility:
Males aged 18 or older with CRPC. Prior treatment with testosterone-lowering therapy is required.
Design:
Participants will be screened. They will have blood and urine tests. They will have a CT scan of the chest, abdomen, and pelvis.
They will continue to receive hormone therapy for prostate cancer.
Participants will come to the NIH clinic once a week for the first 4 weeks. Then they will come once every 2 weeks. Visits will last up to 8 hours. The study will continue up to 3 years.
All participants will receive N-803 once every 2 weeks. The drug is injected just under the skin with a small needle.
Some participants will receive N-803 plus another drug (brachyury vaccine). This drug is also injected under the skin with a small needle.
Some participants will receive N-803 plus a different drug (bintrafusp alfa) once every 2 weeks. This drug is given through a tube attached to a needle placed in a vein in the arm.
Some participants may receive all 3 drugs.
Participants will have imaging scans every 12 weeks.
详细描述
BACKGROUND:
- Prostate cancer is poorly recognized by T cells. Lack of an immune response is one explanation for the lower response rates (<15%) observed with anti-PD-1/PD-L1 therapies for prostate cancer.
- BN-Brachyury is a novel recombinant vector-based therapeutic cancer vaccine designed to induce an enhanced immune response against brachyury, which is overexpressed in many solid tumor types, including prostate adenocarcinoma. BN-Brachyury collectively refers to the priming doses (MVA-BN-Brachyury) and the boost doses (FPV-Brachyury) of the vaccine platform.
- Bintrafusp alfa is a bifunctional fusion protein consisting of an anti-programmed death ligand 1 (PD-L1) antibody and the extracellular domain of transforming growth factor beta (TGF-beta) receptor type 2, a TGF-beta trap. Bintrafusp alfa can also mediate antibody-dependent cellular cytotoxicity in vitro.
- N-803 is an IL-15/IL-15Ralpha superagonist complex that can enhance natural killer (NK) cell-mediated antibody-dependent cellular cytotoxicity (ADCC) and T-cell cytotoxicity.
- Synergistic anti-tumor effects have been observed in vitro when combining bintrafusp alfa and N-803, and in vivo when combining these agents with tumor vaccine in animal models.
- Given the high response rate of 46% seen thus far with the combination of BN-Brachyury, bintrafusp alfa, and N-803 in Arm 2.2A of QuEST1 trial suggests that it is important to determine the relative contribution of each agent in order to determine if a subset of these agents can be used while preserving efficacy and minimizing toxicity. In particular, because the combination of bintrafusp alfa with BN-Brachyury did not produce a significant response rate until N-803 was added, the objective of this Confirmatory QuEST1 trial (ConQuEST) is to investigate the impact of N-803 alone or in an unstudied combination with either BN-Brachyury or bintrafusp alfa.
- This trial offers a means to enhance response rates in castration-resistant prostate cancer (CRPC) on a potentially shorter timeline than with that of traditional trial designs.
OBJECTIVE:
-To determine the clinical efficacy of N-803 alone or in combination with brachyury vaccine or bintrafusp alfa among participants with CRPC
ELIGIBILITY:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Arm 3
N-803 + bintrafusp alfa (+ BN-Brachyury if progression beyond 12 weeks)
干预措施: N-803 (Drug)
Arm 1
N-803 + BN-Brachyury (+ bintrafusp alfa if progression beyond 12 weeks)
干预措施: N-803 (Drug)
Arm 1
N-803 + BN-Brachyury (+ bintrafusp alfa if progression beyond 12 weeks)
干预措施: BN-Brachyury (Biological)
Arm 2
N-803 (+ BN-Brachyury + bintrafusp alfa if progression beyond 12 weeks)
干预措施: N-803 (Drug)
Arm 3
N-803 + bintrafusp alfa (+ BN-Brachyury if progression beyond 12 weeks)
干预措施: Bintrafusp alfa (Drug)
结局指标
主要结局
Clinical Efficacy of N-803 alone or in combination with brachyury vaccine or bintrafusp alfa
时间窗: 12 weeks
In each arm, the fraction who experience a response by 12 weeks will be noted and reported along with a 95% confidence interval.
次要结局
- Duration of response(3 years)
- Radiographic response(3 years)
- Safety profile of N-803 alone or in combination with brachyury vaccine or bintrafusp alfa(3 years)