A Phase 1, Multicenter, Open-label, Dose-Exploration and Dose-Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 650 in Subjects With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 66
- 试验地点
- 22
- 主要终点
- Number of Participants with Serious Adverse Events (SAEs)
研究概览
简要总结
To evaluate the safety and tolerability of AMG 650 in adult participants and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female ≥ 18 years old
- •Triple Negative Breast Cancer participants only: Participant must have histologically or cytologically confirmed metastatic or locally recurrent estrogen receptor (ER)-negative (<1% by immunohistochemistry [IHC]), progesterone receptor (PR)-negative (<1% IHC) and human epidermal growth factor receptor 2 (Her2)-negative (either fluorescent in situ hybridisation [FISH] negative, 0 or 1+ by IHC, or IHC2+ and FISH negative per ASCO/CAP definition) breast cancer. Participant must be relapsed/refractory to at least one line of systemic chemotherapy in the metastatic setting (excluding neoadjuvant or adjuvant chemotherapies) or intolerant of existing therapy(ies) known to provide clinical benefit or have no other available treatment options. Prior exposure to an immune checkpoint inhibitor is allowed.
- •Platinum-Resistant High Grade Serous Ovarian Cancer, primary peritoneal cancer and/or fallopian-tube cancer participants only: Participant must have histologically or cytologically confirmed diagnosis of metastatic or unresectable high grade serous ovarian cancer, with platinum-resistance defined as progression during or within 6 months of a platinum-containing regimen, with no other treatment option available. Prior exposure to platinum-resistant recurrence therapy is allowed.
- •Serous Endometrial Cancer participants only (Dose Exploration only): Participant must have histologically or cytologically confirmed diagnosis of metastatic or recurrent serous endometrial cancer, and be relapsed/refractory to at least one line of systemic therapy in the metastatic/recurrent setting or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
- •Participants with advanced or metastatic solid tumor with TP53MUT (Dose Exploration only, as assessed by local testing) that is unresectable and relapsed/refractory to at least one line of systemic chemotherapy or intolerant.
- •TNBC participants only (Dose Expansion): Progressed on no more than 3 prior lines of systemic therapy for locally advanced or metastatic disease (not including adjuvant or neo-adjuvant). Systemic therapy with poly ADP ribose polymerase (PARP) inhibitor will be counted as one line of therapy.
- •HGSOC participants only (Dose Expansion): Progressed on no more than 5 prior lines of systemic therapy for locally advanced or metastatic disease (not including adjuvant or neo-adjuvant). Systemic therapy with (PARP) inhibitor will be counted as one line of therapy. Induction followed by maintenance will be counted as one line of therapy.
排除标准
- •Untreated or symptomatic brain metastases and leptomeningeal disease (exception: benign asymptomatic tumors are permitted).
- •Current primary CNS tumor, hematological malignancies or lymphoma.
- •Uncontrolled pleural effusions(s), pericardial effusion, or ascites.
- •Gastrointestinal (GI) tract disease causing the inability to take oral medication.
研究组 & 干预措施
Dose Exploration Phase
Participants will receive AMG 650 in 1 of 3 alternative schedules. The maximum tolerated dose (MTD) of each schedule will be estimated using isotonic regression (Ji et al, 2010). The Recommended Phase 2 Dose (RP2D) may be identified based on emerging safety, efficacy, and pharmacodynamics (PD) data prior to reaching an MTD.
干预措施: AMG 650 (Drug)
Dose Expansion Phase Group 1: TNBC
Participants with locally advanced or metastatic triple negative breast cancer (TNBC), will be administered with the preliminary RP2D identified from the dose exploration part of the study.
干预措施: AMG 650 (Drug)
Dose Expansion Phase Group 2: HGSOC
Participants with locally advanced or metastatic high grade serous ovarian cancer (HGSOC), will be administered with the preliminary RP2D identified from the dose exploration part of the study.
干预措施: AMG 650 (Drug)
结局指标
主要结局
Number of Participants with Serious Adverse Events (SAEs)
时间窗: Up to 24 months
Number of Participants with Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to 24 months
Number of Participants with Treatment-related Adverse Events
时间窗: Up to 24 months
Number of Participants with Dose Limiting Toxicities (DLTs)
时间窗: Up to 12 months
Number of Participants Who Experience a Clinically Significant Change from Baseline in Electrocardiogram (ECGs) Measurement
时间窗: Up to 24 months
Number of Participants Who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Tests
时间窗: Up to 24 months
Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Sign Measurement
时间窗: Up to 24 months
次要结局
- Duration of Response (DOR)(Up to 24 months)
- Time to Progression (TTP)(Up to 24 months)
- Overall Survival (OS)(Up to 24 months)
- Time to Maximum Plasma Concentration (Tmax) of AMG 650(Up to 24 months)
- Time to Response (TTR)(Up to 24 months)
- Objective Response Rate (ORR)(Up to 24 months)
- Progression-free Survival (PFS)(Up to 24 months)
- Clinical Benefit Rate (CBR)(Up to 24 months)
- Maximum Plasma Concentration (Cmax) of AMG 650(Up to 24 months)
- Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval for AMG 650(Up to 24 months)