A Phase 2 Trial of SRF617 in Combination With AB928 (Etrumadenant) and AB122 (Zimberelimab) in Patients With Metastatic Castration-Resistant Prostate Cancer
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 16
- 试验地点
- 9
- 主要终点
- Number of Participants With Response
研究概览
简要总结
This trial will look at the safety and preliminary efficacy of SRF617 in combination with etrumadenant and zimberelimab in patients with metastatic castration-resistant prostate cancer (mCRPC).
详细描述
This is a phase 2, open-label, safety and preliminary efficacy trial in patients with mCRPC using the combination of SRF617, etrumadenant (AB928), and zimberelimab (AB122).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •≥ 18 years of age.
- •Metastatic CRPC with castrate levels of testosterone (≤ 50 ng/dL or ≤ 1.7 nmol/L).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Progressed (by PSA or radiologic criteria) during or following treatment with a novel androgen receptor signaling inhibitor (ARSI, eg, abiraterone, enzalutamide, apalutamide, darolutamide), which may have been given for either hormone-sensitive prostate cancer or CRPC.
- •Received 1 to 2 prior lines of taxane chemotherapy, unless the physician and patient believe the patient is medically ineligible or the patient refuses (ineligibility or refusal must be documented in the source documents).
- •Progressed by PSA or radiologic criteria on or during last therapy for prostate cancer.
- •Measurable or non-measurable disease as per radiographic evaluation. Lesions situated in a previously irradiated area are considered evaluable if progression has been demonstrated in such lesions since radiation.
- •Note: If disease is considered non-measurable, a minimum PSA of 1 ng/dL is required with at least 1 confirmed rise at a minimum of a 1-week interval.
- •Adequate hematologic function, defined as absolute neutrophil count ≥ 1.5 × 109/L, hemoglobin ≥ 9.0 g/dL, and platelet count ≥ 100 × 109/L. Transfusions are permitted to meet hemoglobin and platelet criteria. However, the patient must have a stable hemoglobin level and platelet count for ≥ 2 weeks prior to dosing without transfusion.
- •Adequate renal function, defined as serum creatinine clearance ≥ 30 mL/min per Cockcroft-Gault formula.
- •Total bilirubin ≤ 1.5 × upper limit of normal (ULN) (≤ 3 × ULN if elevated because of Gilbert's syndrome, and ≤ 2 × ULN for patients with known liver metastases).
- •Aspartate aminotransferase and alanine aminotransferase < 2.5 × ULN (< 5 × ULN if liver metastases present).
- •Prothrombin time (PT) or international normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN unless the patient is receiving anticoagulant therapy, in which case PT/INR or aPTT must be within therapeutic range of intended use of anticoagulants.
排除标准
- •Currently participating in or has participated in a trial of an investigational device or has used an investigational device within 21 days before the first dose of study drug.
- •Any component of small cell or neuroendocrine histology.
- •Previously received an anti-CD39 antibody, anti-CD39 targeted therapy, or other agent targeting the adenosine pathway.
- •Prior treatment with programmed death-ligand 1 (PD-L1)/programmed death receptor-1 (PD-1) inhibitors.
- •Prior treatment with ≥ 3 lines of taxane chemotherapy administered as a single agent or as part of a combination regimen.
- •Symptomatic or untreated brain metastases (including leptomeningeal metastases). Patients previously treated for brain metastases must be at least 4 weeks from completion of radiation treatment with follow-up imaging showing no progression.
- •Current pneumonitis with or without steroid requirement or history of pneumonitis requiring steroids.
- •Another malignancy other than prostate within 2 years of trial entry, except for those with a low risk of spreading or negligible risk of death such as non-melanoma skin cancer or Ta superficial bladder cancer.
- •Active autoimmune disease that has required systemic treatment in past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs).
- •Medical conditions requiring chronic steroid (ie, > 10 mg/day of prednisone or its equivalent).
- •Note: Replacement therapy (eg, levothyroxine, insulin, or physiologic corticosteroid replacement therapy for thyroid, adrenal, or pituitary insufficiency) is allowed.
- •Administration of a live attenuated vaccine within 6 weeks before the first dose of study drug.
- •Exception: Health Authority approved COVID-19 vaccines are permitted.
- •Any gastrointestinal condition that would preclude the use of oral medications (eg, difficulty swallowing, nausea, vomiting, or malabsorption).
研究组 & 干预措施
SRF617 in combination with etrumadenant and zimberelimab
All patients will receive SRF617 administered in combination with etrumadenant (AB928) and zimberelimab (AB122).
干预措施: SRF617 (Drug)
SRF617 in combination with etrumadenant and zimberelimab
All patients will receive SRF617 administered in combination with etrumadenant (AB928) and zimberelimab (AB122).
干预措施: etrumadenant (Drug)
SRF617 in combination with etrumadenant and zimberelimab
All patients will receive SRF617 administered in combination with etrumadenant (AB928) and zimberelimab (AB122).
干预措施: zimberelimab (Drug)
结局指标
主要结局
Number of Participants With Response
时间窗: From the date of first dose administration to the end of treatment (maximum exposure: 168 days)
Response was defined as Prostate-Specific Antigen (PSA) decline of ≥ 50% (PSA50) and/or radiographic objective response of Complete Response (CR) or Partial Response (PR) per Prostate Cancer Working Group 3 (PCWG3) Criteria. The number of participants with response shows participants with any one or combination of these response types. * CR: Disappearance of all extranodal target lesions. All pathological lymph nodes must have decreased to \< 10 millimeters (mm) in short axis * PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the Baseline sum of diameters
Number of Participants With Adverse Events (AEs)
时间窗: From date of first dose until 90 days after the last dose of treatment (maximum treatment exposure: 168 days)
An AE was defined as any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious Adverse Events (SAEs) were defined as death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or an important medical event that jeopardized participant and required medical intervention to prevent 1 of the outcomes listed in this definition. A summary of other non-serious AEs and all serious AEs, regardless of causality is located in Reported AE section.
次要结局
- Disease Control Rate (DCR)(From the date of first dose administration to the end of treatment (maximum exposure: 168 days))
- Radiographic Progression Free Survival (PFS)(From the date of first dose administration to the end of treatment (maximum exposure: 168 days))
- Duration of Response (DOR)(From the date of first dose administration to the end of treatment (maximum exposure: 168 days))
- Number of Participants With Response Per PCWG3 Criteria(From the date of first dose administration to the end of treatment (maximum exposure: 168 days))
- Landmark PFS Rate(Months 6 and 12)
- Time to PSA Progression(From the date of first dose administration to the end of treatment (maximum exposure: 168 days))
- Maximum Observed Serum Concentration of SRF617 (Cmax)(From the date of first dose administration to the end of treatment (maximum exposure: 168 days))
- Number of Participants With PSA50 Response(From the date of first dose administration to the end of treatment (maximum exposure: 168 days))
- Number of Participants With PSA Decline of ≥ 30% (PSA30) Response(From the date of first dose administration to the end of treatment (maximum exposure: 168 days))
- Number of Participants With Symptomatic Skeletal Events (SSEs)(From date of first dose until 90 days after the last dose of treatment (maximum treatment exposure: 168 days))
- Minimum Observed Serum Concentration of SRF617 Prior to Administration of Subsequent Dose (Cmin)(From the date of first dose administration to the end of treatment (maximum exposure: 168 days))
- Number of Participants With Antidrug Antibodies (ADAs)(From the date of first dose administration to the end of treatment (maximum exposure: 168 days))