A Phase 1b/2, Open-Label, Randomized Platform Study Evaluating the Efficacy and Safety of AB928-Based Treatment Combinations in Patients With Metastatic Castrate Resistant Prostate Cancer
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 173
- 试验地点
- 19
- 主要终点
- Incidence and Severity of AEs and Serious Adverse Events (SAEs) in Stage 1
研究概览
简要总结
This is a Phase 1b/2, open-label, multicenter platform trial to evaluate the antitumor activity and safety of etrumadenant (AB928)-based combination therapy in participants with metastatic castrate resistant prostate cancer (mCRPC).
详细描述
This study has several treatment arms and each treatment arm has 2 stages. During Stage 1 - Etrumadenant plus zimberelimab (AB122) alone, etrumadenant plus zimberelimab with or without a standard of care treatment (enzalutamide or docetaxel), or etrumadenant plus AB680 with or without zimberelimab, or etrumadenant plus Sacituzumab govitecan (SG) alone or etrumadenant plus zimberelimab plus SG will be administered to participants with mCRPC.
During Stage 2 - Additional participants with mCRPC may receive an etrumadenant-based combination therapy evaluated in Stage 1 or, a standard of care treatment.
A pharmacokinetic (PK) Sub-Study (etrumadenant plus zimberelimab) will be conducted separately.
Treatment may continue until unacceptable toxicity or progressive disease, or other reasons specified in the protocol.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Male participants; age ≥ 18 years
- •Metastatic castrate-resistant prostate cancer while on anti-androgen treatment with castrate levels of testosterone (≤1.7 nanomoles per liter [nmol/L] or 50 nanograms per deciliter [ng/dL])
- •Measurable or non-measurable disease as per radiographic evaluation
- •Participants with measurable disease may require a fresh tumor biopsy at study entry
- •Eastern Cooperative Oncology Group (ECOG) Performance status of 0 or 1
- •Life expectancy of at least 3 months
- •Adequate hematologic and end-organ function
- •Human immunodeficiency virus (HIV), Hepatitis B, and C test results negative prior to first study treatment
- •Inclusion Criteria for Participants receiving an enzalutamide-containing treatment
- •Disease progression after prior treatment with abiraterone
- •Inclusion Criteria for Participants receiving a docetaxel-containing treatment
- •Disease progression after prior androgen synthesis inhibitor therapy
- •Inclusion Criteria for all other Participants
- •Disease progression after prior androgen synthesis inhibitor treatment and up to 2 prior lines of taxane chemotherapy
排除标准
- •Prior treatment with immune checkpoint blockade therapy
- •Prior anticancer treatment including approved agents, systemic radiotherapy, or investigational therapy, within 2-4 weeks prior first study treatment
- •Corrected QT interval (QTc) ≥480 msec using Fredericia's QT correction formula (based on an average of triplicate recordings)
- •Prior allogeneic stem cell or solid organ transplantation
- •Prior treatment with drugs that stimulate the immune system within 4 weeks prior to first study treatment
- •Prior treatment with drugs that suppress the immune system within 2 weeks prior to first study treatment
- •Received a live, attenuated vaccine within 4 weeks prior to first study treatment, or may need to receive a vaccine during study treatment
- •Presence of metastases in the brain or cancer spreading into the cerebrospinal fluid - CSF (leptomeningeal disease)
- •Prior pulmonary fibrosis, pneumonia, or pneumonitis
- •Cancer other than prostate within 2 years prior to study entry, except for some cancers with a low risk of spreading like non-melanoma skin
- •Prior treatment with an agent targeting the adenosine pathway
- •No oral or IV antibiotics within 2 weeks prior to first study treatment
- •No severe infection within 4 weeks prior to first study treatment
- •No clinically significant cardiac disease
- •Inability to swallow medications
- •Exclusion Criteria for Participants receiving an enzalutamide-containing treatment
- •Prior treatment with docetaxel, cabazitaxel, or other taxane chemotherapy (prior docetaxel [up to 6 cycles] for hormone-sensitive prostate cancer is allowed if the last dose was at least 6 months prior to study treatment initiation)
- •Prior treatment with enzalutamide or similar therapy other than abiraterone
- •Active or history of autoimmune disease or immune deficiency
- •History of severe allergic reactions to antibody therapy
- •Concomitant use of a medication prohibited by the protocol (including certain transporter substrates as well as known strong CYP3A4 inducers and CYP3A4 inhibitors) within 4 weeks prior to and throughout study treatment
- •Exclusion Criteria for Participants receiving a docetaxel-containing treatment
- •Prior treatment with docetaxel, cabazitaxel, or other taxane chemotherapy
- •Active or history of autoimmune disease or immune deficiency
- •History of severe allergic reactions to antibody therapy
- •Concomitant use of a medication prohibited by the protocol (including certain transporter substrates as well as known strong CYP3A4 inducers and CYP3A4 inhibitors) within 4 weeks prior to and throughout study treatment
- •Exclusion Criteria for all other Participants
- •Prior treatment with docetaxel, cabazitaxel, topoisomerase 1 inhibitors, or other taxane chemotherapy
- •Active or history of autoimmune disease or immune deficiency
- •History of severe allergic reactions to antibody therapy
- •Concomitant use of a medication prohibited by the protocol (including certain transporter substrates as well as known strong CYP3A4 inducers and CYP3A4 inhibitors) within 4 weeks prior to and throughout study treatment
研究组 & 干预措施
Stage 1: Etrumadenant + zimberelimab PK Sub-Study
Participants will receive oral etrumadenant in combination with IV zimberelimab
干预措施: Etrumadenant (Drug)
Stage 1 and 2: Etrumadenant + zimberelimab + enzalutamide
Participants will receive oral etrumadenant in combination with intravenous (IV) zimberelimab and standard oral enzalutamide
干预措施: Etrumadenant (Drug)
Stage 1 and 2: Etrumadenant + zimberelimab + enzalutamide
Participants will receive oral etrumadenant in combination with intravenous (IV) zimberelimab and standard oral enzalutamide
干预措施: Zimberelimab (Drug)
Stage 1 and 2: Etrumadenant + zimberelimab + enzalutamide
Participants will receive oral etrumadenant in combination with intravenous (IV) zimberelimab and standard oral enzalutamide
干预措施: Enzalutamide (Drug)
Stage 2: enzalutamide
Participants will receive standard oral enzalutamide
干预措施: Enzalutamide (Drug)
Stage 1 and 2: Etrumadenant + zimberelimab + docetaxel
Participants will receive oral etrumadenant in combination with IV zimberelimab and standard IV docetaxel
干预措施: Etrumadenant (Drug)
Stage 1 and 2: Etrumadenant + zimberelimab + docetaxel
Participants will receive oral etrumadenant in combination with IV zimberelimab and standard IV docetaxel
干预措施: Zimberelimab (Drug)
Stage 1 and 2: Etrumadenant + zimberelimab + docetaxel
Participants will receive oral etrumadenant in combination with IV zimberelimab and standard IV docetaxel
干预措施: Docetaxel (Drug)
Stage 2: docetaxel
Participants will receive standard dose of IV docetaxel
干预措施: Docetaxel (Drug)
Stage 1 and 2: Etrumadenant + zimberelimab
Oral etrumadenant in combination IV zimberelimab
干预措施: Etrumadenant (Drug)
Stage 1 and 2: Etrumadenant + zimberelimab
Oral etrumadenant in combination IV zimberelimab
干预措施: Zimberelimab (Drug)
Stage 2: Etrumadenant + zimberelimab + quemliclustat
Participants will receive oral etrumadenant in combination with IV zimberelimab and IV quemliclustat
干预措施: Etrumadenant (Drug)
Stage 2: Etrumadenant + zimberelimab + quemliclustat
Participants will receive oral etrumadenant in combination with IV zimberelimab and IV quemliclustat
干预措施: Zimberelimab (Drug)
Stage 2: Etrumadenant + zimberelimab + quemliclustat
Participants will receive oral etrumadenant in combination with IV zimberelimab and IV quemliclustat
干预措施: Quemliclustat (Drug)
Stage 2: Etrumadenant + quemliclustat
Participants will receive oral etrumadenant in combination with IV quemliclustat
干预措施: Etrumadenant (Drug)
Stage 2: Etrumadenant + quemliclustat
Participants will receive oral etrumadenant in combination with IV quemliclustat
干预措施: Quemliclustat (Drug)
Stage 1: Etrumadenant + zimberelimab PK Sub-Study
Participants will receive oral etrumadenant in combination with IV zimberelimab
干预措施: Zimberelimab (Drug)
Stage 1 and 2: Etrumadenant + SG
Participants will receive oral etrumadenant in combination with IV SG.
干预措施: Etrumadenant (Drug)
Stage 1 and 2: Etrumadenant + SG
Participants will receive oral etrumadenant in combination with IV SG.
干预措施: SG (Drug)
Stage 1 and 2: Etrumadenant + Zimberelimab + SG
Participants will receive oral etrumadenant in combination with IV zimberelimab and SG.
干预措施: Etrumadenant (Drug)
Stage 1 and 2: Etrumadenant + Zimberelimab + SG
Participants will receive oral etrumadenant in combination with IV zimberelimab and SG.
干预措施: Zimberelimab (Drug)
Stage 1 and 2: Etrumadenant + Zimberelimab + SG
Participants will receive oral etrumadenant in combination with IV zimberelimab and SG.
干预措施: SG (Drug)
结局指标
主要结局
Incidence and Severity of AEs and Serious Adverse Events (SAEs) in Stage 1
时间窗: From first dose date to 90 days after the last dose (approximately 1.5 years)
Objective Response Rate (ORR) in Stage 1 and 2
时间窗: From study enrolment until participant discontinuation, or first occurrence of progressive disease, or death from any cause, whichever occurs first (approximately 3-5 years)
ORR defined as the composite proportion of participants with a Prostate Specific Antigen (PSA) and/or radiographic complete response (CR) and partial response (PR) determined by the investigator according to the Prostate Cancer Working Group 3 (PCWG3) criteria
次要结局
- Percentage of participants with a PSA response in Stage 1 and 2(From study enrollment until disease progression or loss of clinical benefit (approximately 3-5 years))
- Percentage of participants with Radiographic Response in Stage 1 and 2(From study enrollment until disease progression or loss of clinical benefit (approximately 3-5 years))
- Serum/Plasma Concentration for etrumadenant and zimberelimab when administered as part of a combination regimen with docetaxel in Stage 1 and 2(Recorded at baseline (enrollment), during the first 5 months of treatment and 3 additional timepoints in the first year of treatment. (approximately 1.5 years))
- Serum/Plasma Concentration for etrumadenant and zimberelimab when administered as part of a combination regimen in Stage 1 and 2(Recorded at baseline (enrollment), during the first 5 months of treatment and 3 additional timepoints in the first year of treatment. (approximately 1.5 years))
- Percentage of participants with anti-drug antibodies to zimberelimab in Stage 1 and 2(Recorded at baseline (enrollment), during the first 4 months of treatment, 4 additional timepoints in the first year of treatment, and at end of treatment. (approximately 1.5 years))
- Percentage of Participants with Disease Control Rate in Stage 1 and 2(From study enrollment until disease progression or loss of clinical benefit (approximately 3-5 years))
- Serum/Plasma Concentration for etrumadenant, zimberelimab, and enzalutamide when administered as part of a combination regimen in Stage 1 and 2.(Recorded at baseline (enrollment), during the first 5 months of treatment and 3 additional timepoints in the first year of treatment. (approximately 1.5 years))
- Serum/Plasma Concentration for etrumadenant, zimberelimab, and AB680 when administered as part of a combination regimen in Stage 1 and 2(Recorded at baseline (enrollment), during the first 5 months of treatment and 3 additional timepoints in the first year of treatment. (approximately 1.5 years))
- Serum/Plasma Concentration for etrumadenant and AB680 when administered as part of a combination regimen in Stage 1 and 2.(Recorded at baseline (enrollment), during the first 5 months of treatment and 3 additional timepoints in the first year of treatment. (approximately 1.5 years))
- Incidence and severity of AEs and serious adverse events (SAEs) in Stage 2(From first dose date to 90 days after the last dose (approximately 3-5 years))