An Open-label, Multi-center, Phase I/II Study of GVV858 as a Single Agent and in Combination With Endocrine Therapy in Patients With Advanced Hormone Receptor Positive, HER2- Negative Breast Cancer and Other Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 205
- 试验地点
- 17
- 主要终点
- Phase I and phase II: Dose intensity
研究概览
简要总结
Phase I: Characterize safety and tolerability of GVV858 as a single agent and in combination with fulvestrant or letrozole. Identify dose range for optimization/recommended dose for further clinical evaluation.
Phase II: Further characterize the safety and tolerability of GVV858 in combination with fulvestrant in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced breast cancer.
详细描述
This is a first-in-human, open-label, phase I/II, multi-center study consisting of a GVV858 single agent treatment arm in patients with advanced HR+/HER2- breast cancer, other advanced solid tumors harboring CCNE1 amplification, and metastatic castration-resistant prostate cancer, and a combination treatment arm of GVV858 with fulvestrant or letrozole in patients with advanced HR+/HER2- breast cancer. Single agent escalation may be followed by an expansion part stratified by disease indication. The escalation of the fulvestrant combination arm may continue into a randomized, open label, Phase II with optional dose optimization in advanced HR+/HER2- breast cancer patients.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years old.
- •Patients with one of the following histologically or cytologically confirmed advanced cancers:
- •Phase I (patients with one of the following cancers, from whom no standard therapy is available or appropriate in the judgment of the investigator):
- •HR+/HER2- advanced breast cancer (aBC) with disease progression on or following at least one line of hormone-based therapy in combination with a CDK4/6i and at least one additional line of systemic therapy for metastatic disease.
- •Locally advanced or metastatic cancer with a CCNE1 amplification. For dose expansion only: no more than 3 prior lines of therapy for advanced or metastatic disease.
- •Metastatic castration-resistant prostate adenocarcinoma, with no documented neuroendocrine component, castrate level of testosterone, and no more than 3 prior lines of systemic therapy for metastatic disease.
- •HR+/HER2- aBC with disease progression on or after an endocrine therapy in combination, with a CDK4/6 inhibitor for advanced disease with no more than 2 lines of endocrine therapy and no prior cytotoxic chemotherapy or antibody-drug-conjugate for advanced disease.
- •- Measurable disease as determined by RECIST v1.
- •BC only: If no measurable disease is present, then at least one predominantly lytic bone lesion must be present that can be accurately assessed at baseline and is suitable for repeated assessment.
- •metastatic Castration-Resistant Prostate Cancer (mCRPC) only: If no measurable disease is present per PCWG3 modified RECIST, then at least 1 metastatic lesion must be present on bone scan imaging.
排除标准
- •Patients with inadequate bone marrow and/or organ functions with out-of-range laboratory values.
- •Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormality including myocardial infarction (MI), coronary artery bypass graft (CABG), long QT syndrome, or risk factors for Torsades de Pointes (TdP).
- •Presence of symptomatic central nervous system (CNS) metastases or CNS metastases that require local therapy or increasing doses of corticosteroids within 2 weeks prior to study entry.
- •Patients with symptomatic visceral disease, including visceral crisis.
- •For patients with BC: Patient is concurrently using hormone replacement therapy.
- •Women of childbearing potential who are unwilling to use highly effective contraception methods, pregnant or nursing women.
- •Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
GVV858 in combination with fulvestrant (Arm B)
Phase I
干预措施: GVV858 (Drug)
GVV858 Single Agent (Arm A)
Phase I
干预措施: GVV858 (Drug)
GVV858 in combination with fulvestrant (Arm D)
Phase II, recommended dose regimen 1
干预措施: GVV858 (Drug)
GVV858 in combination with letrozole (Arm C)
Phase I
干预措施: GVV858 (Drug)
GVV858 in combination with fulvestrant (Arm E)
Phase II, recommended dose regimen 2, optional dose optimization
干预措施: GVV858 (Drug)
GVV858 in combination with fulvestrant (Arm E)
Phase II, recommended dose regimen 2, optional dose optimization
干预措施: Fulvestrant (Drug)
GVV858 in combination with letrozole (Arm C)
Phase I
干预措施: Letrozole (Drug)
GVV858 in combination with fulvestrant (Arm D)
Phase II, recommended dose regimen 1
干预措施: Fulvestrant (Drug)
GVV858 in combination with fulvestrant (Arm B)
Phase I
干预措施: Fulvestrant (Drug)
结局指标
主要结局
Phase I and phase II: Dose intensity
时间窗: Up to approximately 2 years
The dose intensity of each study drug is computed as the ratio of actual cumulative dose received and actual duration of exposure.
Phase I: Incidence and severity of dose-limiting toxicities (DLTs)
时间窗: 28 days
Number of participants with DLTs. A DLT is defined as an adverse event or abnormal laboratory value of Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or higher, unless clearly and inconvertibly assessed as due to disease progression, inter-current illness/injury, concomitant medications, or extraneous causes, that occurs within the first 28 days of treatment in the Phase 1 part. Other clinically significant toxicities may be considered to be DLTs, even if not CTCAE grade 3 or higher.
Phase I and phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
时间窗: Up to approximately 2 years
Number of participants with AEs and SAEs, including changes in vital signs, electrocardiograms (ECGs) and laboratory values qualifying and reported as AEs.
Phase I and phase II: Frequency of dose interruptions, reductions and discontinuations
时间窗: Up to approximately 2 years
Number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) as a measure of tolerability.
次要结局
- Phase I and II: Peak plasma concentration (Cmax) of GVV858(Cycle 1 Day 1 and/or Day 21: From pre-dose up to maximum 24 hours post dose. The duration of one cycle is 28 days.)
- Phase I and II: Time to reach peak plasma concentration (Tmax) of GVV858(Cycle 1 Day 1 and/or Day 21: From pre-dose up to maximum 24 hours post dose. The duration of one cycle is 28 days.)
- Phase I and II: Area under the plasma concentration-time curve (AUC) of GVV858(Cycle 1 Day 1 and/or Day 21: From pre-dose up to maximum 24 hours post dose. The duration of one cycle is 28 days.)
- Phase I and Phase II: Disease control rate (DCR)(Up to approximately 2 years)
- Phase I and Phase II: Best overall response (BOR)(Up to approximately 2 years)
- Phase I and Phase II: Overall response rate (ORR)(Up to approximately 2 years)
- Phase I and Phase II: Clinical benefit rate (CBR)(Up to approximately 2 years)
- Phase I and Phase II: Progression free survival (PFS)(Up to approximately 2 years)
- Phase II: Duration of response (DOR)(Up to approximately 2 years)