A Phase I/II Study of Immunotherapy Combination BN-Brachyury Vaccine, M7824, N-803 and Epacadostat (QuEST1)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 59
- 试验地点
- 1
- 主要终点
- Clinical Benefit With Any of a Set of 3 Possible Treatments for Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Reported With an 80% Confidence Interval
研究概览
简要总结
Background:
Immunotherapy drugs help the body to fight cancer. Scientists think that combining some of these drugs will make them work better than when used alone. This may be true for many types of cancer, including castration-resistant prostate cancer (CRPC).
Objective:
To test if any of the combinations of drugs below have anti-prostate cancer activity and to test if they are safe.
- Bavarian-Nordic (BN)-brachyury, bintrafusp alfa (M7824).
- Bavarian-Nordic (BN)-brachyury, bintrafusp alfa (M7824) + Anktiva (N-803).
- Bavarian-Nordic (BN)-brachyury, bintrafusp alfa (M7824) + Anktiva (N-803) + Epacadostat.
Eligibility:
People ages 18 and older with CRPC or another metastatic cancer
Design:
Participants will be screened with:
- Medical history
- Physical exam
- Computed tomography (CT) or magnetic resonance imaging (MRI) scans
- Possible bone imaging
- Blood, urine, and heart tests
- Possible tumor biopsy
Participants will be treated with a 2-, 3- or 4-drug combinations of the following study drugs in 2-week cycles:
- Participants will receive M7824 by intravenous (IV) once every 2 weeks.
- Participants will receive N-803 by injection once every 2 weeks. They will record any skin changes at the injection site in a diary.
- Participants will receive BN-brachyury as 4 injections to different limbs. They will get the first 3 doses 2 weeks apart. Then they will get doses every 4 weeks for 6 months, then every 3 months for 2 years, then every 6 months.
- Participants will take Epacadostat orally every 12 hours. They will keep a pill diary.
Participants will have physical exams and blood and urine tests at the start of each cycle. They may have scans every 12 weeks.
Participants will continue treatment until their disease gets worse or they cannot tolerate the side effects.
Participants will have a follow-up visit 4-5 weeks after they stop treatment. They will have a physical exam and blood tests. They may be asked to return for scans every 3 months.
详细描述
Background:
- Programmed cell death protein 1 (PD-1)/programmed death ligand 1 (PD-L1) signaling appears to be a major inhibitor of activated T cell anti-tumor immune responses. The rapid, deep and durable responses seen in various malignancies with PD-1/PD-L1 targeted agents demonstrate that blockade of this axis is key to facilitating immune responses within the tumor microenvironment (TME).
- 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.
- Increasing response rates will likely require therapeutic nullification of multiple immune deficits by combining immunotherapies that generate tumor-specific T cells (vaccine), dampen the inhibitory milieu of the TME, and enhance T and natural killer (NK) cell activity within the TME.
- A quick efficacy seeking trial, utilizing sequential arms offers a means to identify signals of activity for combinations of immunotherapy, added sequentially, in castration resistant prostate cancer (CRPC) participants.
- Bavarian Nordic (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 (modified vaccinia Ankara (MVA)-BN-Brachyury) and the boost doses (fowlpox virus (FPV)-Brachyury) of the vaccine platform.
- bintrafusp alfa (M7824) 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. M7824 can also mediate antibody-dependent cellular cytotoxicity in vitro.
- Anktiva (N-803) is an interleukin 15 (IL-15)/IL-15R alpha superagonist complex that can enhance NK cell mediated antibody-dependent cell-mediated cytotoxicity (ADCC) and T-cell cytotoxicity.
- Synergistic anti-tumor effects have been observed in vitro when combining M7824 and N-803, and in vivo when combining these agents with tumor vaccine in animal models.
- Indoleamine 2,3-dioxygenase 1 (IDO1) is overexpressed in many solid tumors and can contribute to immune escape by tumor cells. INCB024360 (Epacadostat) is an IDO1 inhibitor under investigation in combination with different immunotherapies in treatment of various malignancies.
- In treating of CRPC, we hypothesize that these agents and their effects will be complementary. Tumor-specific T cells generated by vaccine may become more functional in a TME following treatment with M7824 and Epacadostat. N-803 can further enhance the activity of antigen-specific T cells as well as NK cells.
Objective:
-To determine if there is clinical benefit to any of a set of 3 possible treatments for participants with CRPC:
- BN-Brachyury + M7824
- BN-Brachyury + M7824 + N-803
- BN-Brachyury + M7824 + N-803 + Epacadostat
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- All
- 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 1.1 Bintrafusp alfa (M7824) + Anktiva (N-803)
Bintrafusp alfa (M7824) + Anktiva (N-803)
干预措施: M7824 (Biological)
Arm 1.1 Bintrafusp alfa (M7824) + Anktiva (N-803)
Bintrafusp alfa (M7824) + Anktiva (N-803)
干预措施: N-803 (Drug)
Arm 1.1 Bintrafusp alfa (M7824) + Anktiva (N-803)
Bintrafusp alfa (M7824) + Anktiva (N-803)
干预措施: Acetaminophen (Drug)
Arm 1.1 Bintrafusp alfa (M7824) + Anktiva (N-803)
Bintrafusp alfa (M7824) + Anktiva (N-803)
干预措施: Ibuprofen (Drug)
Arm 1.1 Bintrafusp alfa (M7824) + Anktiva (N-803)
Bintrafusp alfa (M7824) + Anktiva (N-803)
干预措施: Naproxen (Drug)
Arm 1.1 Bintrafusp alfa (M7824) + Anktiva (N-803)
Bintrafusp alfa (M7824) + Anktiva (N-803)
干预措施: Benadryl (Other)
Arm 1.1 Bintrafusp alfa (M7824) + Anktiva (N-803)
Bintrafusp alfa (M7824) + Anktiva (N-803)
干预措施: EKG (Diagnostic Test)
Arm 1.1 Bintrafusp alfa (M7824) + Anktiva (N-803)
Bintrafusp alfa (M7824) + Anktiva (N-803)
干预措施: Bone scan (Diagnostic Test)
Arm 1.1 Bintrafusp alfa (M7824) + Anktiva (N-803)
Bintrafusp alfa (M7824) + Anktiva (N-803)
干预措施: CT chest, abdomen and pelvis (Diagnostic Test)
Arm 1.1 Bintrafusp alfa (M7824) + Anktiva (N-803)
Bintrafusp alfa (M7824) + Anktiva (N-803)
干预措施: MRI (Diagnostic Test)
Arm 2.1A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
干预措施: M7824 (Biological)
Arm 2.1A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
干预措施: MVA-BN-Brachyury (Biological)
Arm 2.1A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
干预措施: FPV-Brachyury (Biological)
Arm 2.1A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
干预措施: Acetaminophen (Drug)
Arm 2.1A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
干预措施: Ibuprofen (Drug)
Arm 2.1A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
干预措施: Naproxen (Drug)
Arm 2.1A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
干预措施: Benadryl (Other)
Arm 2.1A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
干预措施: EKG (Diagnostic Test)
Arm 2.1A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
干预措施: Bone scan (Diagnostic Test)
Arm 2.1A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
干预措施: CT chest, abdomen and pelvis (Diagnostic Test)
Arm 2.1A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIA
干预措施: MRI (Diagnostic Test)
Arm 2.1B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
干预措施: M7824 (Biological)
Arm 2.1B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
干预措施: MVA-BN-Brachyury (Biological)
Arm 2.1B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
干预措施: FPV-Brachyury (Biological)
Arm 2.1B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
干预措施: Acetaminophen (Drug)
Arm 2.1B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
干预措施: Ibuprofen (Drug)
Arm 2.1B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
干预措施: Naproxen (Drug)
Arm 2.1B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
干预措施: Benadryl (Other)
Arm 2.1B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
干预措施: EKG (Diagnostic Test)
Arm 2.1B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
干预措施: Bone scan (Diagnostic Test)
Arm 2.1B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
干预措施: CT chest, abdomen and pelvis (Diagnostic Test)
Arm 2.1B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury during phase IIB
干预措施: MRI (Diagnostic Test)
Arm 2.2A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
干预措施: M7824 (Biological)
Arm 2.2A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
干预措施: N-803 (Drug)
Arm 2.2A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
干预措施: MVA-BN-Brachyury (Biological)
Arm 2.2A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
干预措施: FPV-Brachyury (Biological)
Arm 2.2A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
干预措施: Acetaminophen (Drug)
Arm 2.2A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
干预措施: Ibuprofen (Drug)
Arm 2.2A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
干预措施: Naproxen (Drug)
Arm 2.2A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
干预措施: Benadryl (Other)
Arm 2.2A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
干预措施: EKG (Diagnostic Test)
Arm 2.2A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
干预措施: Bone scan (Diagnostic Test)
Arm 2.2A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
干预措施: CT chest, abdomen and pelvis (Diagnostic Test)
Arm 2.2A Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIA
干预措施: MRI (Diagnostic Test)
Arm 2.2B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
干预措施: M7824 (Biological)
Arm 2.2B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
干预措施: N-803 (Drug)
Arm 2.2B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
干预措施: MVA-BN-Brachyury (Biological)
Arm 2.2B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
干预措施: FPV-Brachyury (Biological)
Arm 2.2B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
干预措施: Acetaminophen (Drug)
Arm 2.2B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
干预措施: Ibuprofen (Drug)
Arm 2.2B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
干预措施: Naproxen (Drug)
Arm 2.2B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
干预措施: Benadryl (Other)
Arm 2.2B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
干预措施: EKG (Diagnostic Test)
Arm 2.2B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
干预措施: Bone scan (Diagnostic Test)
Arm 2.2B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
干预措施: CT chest, abdomen and pelvis (Diagnostic Test)
Arm 2.2B Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) during phase IIB
干预措施: MRI (Diagnostic Test)
Arm 2.3A M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
干预措施: M7824 (Biological)
Arm 2.3A M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
干预措施: N-803 (Drug)
Arm 2.3A M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
干预措施: MVA-BN-Brachyury (Biological)
Arm 2.3A M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
干预措施: FPV-Brachyury (Biological)
Arm 2.3A M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
干预措施: Epacadostat (Drug)
Arm 2.3A M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
干预措施: Acetaminophen (Drug)
Arm 2.3A M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
干预措施: Ibuprofen (Drug)
Arm 2.3A M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
干预措施: Naproxen (Drug)
Arm 2.3A M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
干预措施: Benadryl (Other)
Arm 2.3A M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
干预措施: EKG (Diagnostic Test)
Arm 2.3A M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
干预措施: Bone scan (Diagnostic Test)
Arm 2.3A M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
干预措施: CT chest, abdomen and pelvis (Diagnostic Test)
Arm 2.3A M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIA
干预措施: MRI (Diagnostic Test)
Arm 2.3B M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
干预措施: M7824 (Biological)
Arm 2.3B M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
干预措施: N-803 (Drug)
Arm 2.3B M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
干预措施: MVA-BN-Brachyury (Biological)
Arm 2.3B M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
干预措施: FPV-Brachyury (Biological)
Arm 2.3B M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
干预措施: Epacadostat (Drug)
Arm 2.3B M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
干预措施: Acetaminophen (Drug)
Arm 2.3B M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
干预措施: Ibuprofen (Drug)
Arm 2.3B M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
干预措施: Naproxen (Drug)
Arm 2.3B M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
干预措施: Benadryl (Other)
Arm 2.3B M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
干预措施: EKG (Diagnostic Test)
Arm 2.3B M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
干预措施: Bone scan (Diagnostic Test)
Arm 2.3B M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
干预措施: CT chest, abdomen and pelvis (Diagnostic Test)
Arm 2.3B M7824 + BN-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
Bintrafusp alfa (M7824) + Bavarian Nordic (BN)-Brachyury + Anktiva (N-803) + Epacadostat during phase IIB
干预措施: MRI (Diagnostic Test)
结局指标
主要结局
Clinical Benefit With Any of a Set of 3 Possible Treatments for Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) Reported With an 80% Confidence Interval
时间窗: From enrollment up to 49 weeks
Objective clinical response and/or prostate-specific antigen (PSA) decline of \>=30% sustained for a minimum of 21 days. Any of these is considered 'clinical benefit.' Objective response was assessed by the response evaluation criteria in solid tumors (RECIST) 1.1. Complete response (CR) is disappearance of all non-target lesions and normalization of tumor marker level. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions. Three treatments evaluated are: Phase II Bavarian Nordic (BN) Brachyury + Bintrafusp alfa (M7824), Phase II Bavarian Nordic (BN) Brachyury + Bintrafusp alfa (M7824) + Anktiva (N-803), and Phase II Bavarian Nordic (BN) Brachyury + Bintrafusp alfa (M7824) + Anktiva (N-803) + Epacadostat.
Clinical Benefit(Objective Response if Measurable Disease by Response Evaluation Criteria in Solid Tumors v1.1)With Any of 3 Possible Treatments for Participants With Metastatic Castration-resistant Prostate Cancer Reported With a 95% Confidence Interval
时间窗: From enrollment up to 49 weeks
Objective response was assessed by the response evaluation criteria in solid tumors (RECIST) 1.1. Complete response (CR) is disappearance of all non-target lesions and normalization of tumor marker level. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. Progressive disease (PD) is at least a 20% increase in the sum of the diameters of target lesions. Three treatments evaluated are: Phase II Bavarian Nordic (BN) Brachyury + Bintrafusp alfa (M7824), Phase II Bavarian Nordic (BN) Brachyury + Bintrafusp alfa (M7824) + Anktiva (N-803), and Phase II Bavarian Nordic (BN) Brachyury + Bintrafusp alfa (M7824) + Anktiva (N-803) + Epacadostat.
Phase I/II: Number of Participants With Grades 3, 4, and/or 5 Serious and/or Non-serious Dose-limiting Toxicities (DLT)
时间窗: Within 21 days of the start of treatment
A DLT is defined as any of the following adverse events (AE) possibly related to study drugs that occur within 21 days of the start of treatment. Adverse events were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Grade 3 is moderate. Grade 4 is life-threatening, and Grade 5 is death related to AE. A DLT is any grade ≥ 4 hematologic toxicity or grade 3 thrombocytopenia with associated bleeding; any grade ≥ 3 non-hematologic toxicity, except for any of the following: transient (≤ 48 hour) grade 3 fatigue, local reactions, flu-like symptoms, fever, headache, or nausea, emesis, and diarrhea; or CTCAE Grade 3 skin toxicity lasting less than five days. A non-serious AE is any untoward medical occurrence. A serious AE is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, or congenital anomaly/birth defect.
次要结局
- 6-month Progression Free Survival (PFS) Probability(6-months)
- Number of Participants With Grades 1, 2, 3, and 4 Non-serious Adverse Events Related to Treatment Treated With Combinations and Bintrafusp Alfa (M7824) + Anktiva (N-803)(3 weeks dose-limiting toxicity (DLT) period)
- Number of Participants With Grades 3, 4, and/or 5 Serious Adverse Events Related to Treatment Treated With Combinations and Bintrafusp Alfa (M7824) + Anktiva (N-803)(3 weeks dose-limiting toxicity (DLT) period)
研究者
James Gulley, M.D.
Principal Investigator
National Cancer Institute (NCI)