A Multicenter, Phase 1, Open-label, Dose-escalation and Expansion Study of AMG 340, a Bispecific Antibody Targeting PSMA in Subjects With Metastatic Castrate-Resistant Prostate Carcinoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- Amgen
- 入组人数
- 42
- 试验地点
- 7
- 主要终点
- Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
This is a phase 1, open-label study evaluating the safety, clinical pharmacology and clinical activity of AMG 340, a PSMA x CD3 T-cell engaging bispecific antibody, in subjects with metastatic castrate-resistant prostate cancer (mCRPC) who have received 2 or more prior lines of therapy. The study consists of 2 parts, a monotherapy dose escalation (Arm A) and a monotherapy dose expansion (Arm B). Once the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) is identified in Arm A, Arm B will be initiated to further characterize the safety, tolerability and pharmacokinetic (PK) profile of the MTD/RP2D dose of AMG 340 monotherapy in subjects with mCRPC.
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 —（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 否
入选标准
- •Pathologically confirmed prostatic adenocarcinoma.
- •History of metastatic disease.
- •Chemically or surgically castrate.
- •Subject has received at least 2 lines of systemic therapy approved for mCRPC, with disease progression on the most recent systemic therapy as defined in Prostate Cancer Working Group 3 (PCWG3) recommendations.
- •Human immunodeficiency virus (HIV), hepatitis B virus (HBV), and/or hepatitis C virus (HCV)-infected subjects that have been cured or who are on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial.
- •An Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤
- •Subject must have adequate heart, liver, bone marrow and kidney function (e.g. estimated glomerular filtration rate [eGFR] ≥ 50 mL/min, aspartate aminotransferase [AST]/alanine aminotransferase [ALT] ≤ 3 x upper limit of normal [ULN], hemoglobin [Hgb] ≥ 9 g/dL (without blood transfusion within 7 days from screening assessment), platelets ≥ 100,000 / mm^3 (without platelet transfusion within 7 days from screening assessment), absolute neutrophil count [ANC] ≥ 1500 / mm^3).
排除标准
- •Subject has been diagnosed with or treated for another malignancy within the past 2 years whose natural history or treatment may interfere with the safety or efficacy assessment of the investigational regimen.
- •History of neuroendocrine differentiation in the subject's disease.
- •Subject has a history of central nervous system (CNS) involvement by their mCRPC. Metastases stemming from bone are allowed.
- •Subject has clinically significant CNS pathology.
- •Subject requires chronic immunosuppressive therapy.
- •Subject has a history of major cardiac abnormalities.
研究组 & 干预措施
Dose Escalation
Sequential dose escalation cohorts are planned until maximum tolerated dose (MTD) is reached or recommended phase 2 dose (RP2D) is identified.
干预措施: AMG 340 (Drug)
Dose Expansion
An expansion cohort in subjects with mCRPC will be enrolled after RP2D is established.
干预措施: AMG 340 (Drug)
结局指标
主要结局
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
时间窗: From enrollment up to and including a maximum of 90 days after last dose of AMG 340; median (min, max) duration was 4.3 (0.5, 27.1) months
An adverse event (AE) was any untoward medical occurrence in a clinical study participant, regardless of a causal relationship with the study treatment. TEAEs included any event occurring after the participant received the study treatment. A treatment-related AE (TRAE) was defined as any TEAE flagged as possibly caused by AMG 340. Clinically significant changes in vital signs, electrocardiograms, and laboratory tests recorded after treatment administration were documented as TEAEs. Serious TEAEs (SAEs) were any untoward medical occurrences after the first dose, irrespective of a causal link to the study treatment, that led to death, were life-threatening, required hospitalization or its prolongation, caused significant disability, resulted in congenital anomalies, or were considered other medically important events.
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
时间窗: Up to approximately Day 21
A DLT was defined as a TEAE that was not unequivocally due to the participant's underlying malignancy or other extraneous cause, and appeared within 21 days from the first dose of AMG 340. AEs considered DLTs were: * Transient (≤72 hours) grade 3 or 4 electrolyte abnormalities, hyperglycemia, nausea/vomiting/diarrhea responsive to treatment. * Alopecia, vitiligo, and grade 3 fatigue lasting \<10 days. * Grade 3 fever lasting ≤24 hours (outside CRS context). * Grade 3 lab abnormalities resolving within 72 hours (or within 7 days for certain enzymes like ALT, GGT, ALP, and lipase). * Grade 3 CRS or TLS unresolved to ≤ grade 1 within 72 hours or any grade 4 CRS/TLS. * Prolonged grade 4 neutropenia (\>5 days) or febrile neutropenia. * Grade 3 thrombocytopenia with bleeding or any grade 4 thrombocytopenia. * Grade 4 anemia. * Grade 5 adverse events. * Lymphopenia is not considered a DLT.
Median Concentration of AMG 340
时间窗: Cohorts 1-5: Days 1 (pre-dose to 6 hours post-dose), 2, 3, 8, and 10; Cohorts 6-10: Days 1 (pre-dose to 6 hours post-dose), 2, 3, 5 (pre-dose to 6 hours post-dose), 6, 7, 8 (pre-dose to 6 hours post-dose), 9, 10
Blood samples for pharmacokinetics (PK) analysis were collected at specific time points. PK parameters were estimated using standard non-compartmental approaches.
次要结局
- Percentage of Participants Who Achieved an Objective Response (OR) Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1(Up to approximately 24 months)
- Overall Survival (OS)(Up to approximately 24 months)
- Prostate Specific Antigen (PSA) Progression Free Survival (PFS)(Up to approximately 24 months)
- Radiographic PFS (rPFS)(Up to approximately 24 months)
- Percentage of Participants With rPFS at 6 Months(6 months)
- Percentage of Participants With a 30% Reduction From Baseline in PSA (PSA30)(Up to approximately 24 months)
- Percentage of Participants With a 50% Reduction From Baseline in PSA (PSA50)(Up to approximately 24 months)
- Percentage of Participants With a 70% Reduction From Baseline in PSA (PSA70)(Up to approximately 24 months)
- Percentage of Participants With a 90% Reduction From Baseline in PSA (PSA90)(Up to approximately 24 months)
- Duration of Response (DOR) Per RECIST 1.1(Up to approximately 24 months)
- Number of Participants With Symptomatic Skeletal Events (SSE)(Up to approximately 24 months)