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
- 2 期
- 状态
- 招募中
- 入组人数
- 55
- 试验地点
- 12
- 主要终点
- Phase I: Safety: Incidence and severity of dose-limiting toxicities (DLTs), adverse events (AEs) and serious adverse events (SAEs), including changes in lab values, vital signs, electrocardiograms (ECGs). Tolerability: Frequency of dose interruptions, reductions, discontinuations, dose intensity.
研究概览
简要总结
Phase I:
To assess the safety and tolerability of GVV858 as a single agent and in combination with fulvestrant or letrozole.
To identify the recommended dose(s) (RD) and/or dose range for optimization (DRO) for further clinical evaluation.
Phase II:
To further characterize the safety and tolerability of GVV858 in combination with fulvestrant.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years old.
- •Phase I, Dose escalation: Patients with one of the following histologically or cytologically confirmed advanced cancers, for whom no standard therapy is available or appropriate in the judgement of the investigator: HR+/HER2- advanced breast cancer (aBC) with disease progression on or following, or have been intolerant to, at least one line of hormone-based therapy in combination with a CDK4/6i for advanced disease (or during or within 12 months of completing adjuvant endocrine therapy (ET) plus CDK4/6i therapy), and at least one additional line of systemic therapy for metastatic disease. Locally advanced or metastatic solid malignancy with CCNE-1 amplification.
- •Phase I, Dose expansion: Patients with one of the following histologically or cytologically confirmed advanced cancers, for whom no standard therapy is available or appropriate in the judgement of the investigator: HR+/HER2- aBC with disease progression on or following, or have been intolerant to, at least one line of hormone-based therapy in combination with a CDK4/6i for advanced disease (or during or within 12 months of completing adjuvant ET plus CDK4/6i therapy), and at least one additional line of systemic therapy for metastatic disease. Advanced or metastatic ovarian cancer (OC) with CCNE-1 amplification, following progression on or after, or intolerance to, standard-of-care (SOC) therapy. Advanced or metastatic gastric or esophageal adenocarcinoma (GEA) with CCNE-1 amplification, following progression on or after, or intolerance to, SOC therapy. Metastatic castration-resistant prostate cancer (mCRPC) with disease progression on or after, or intolerance to, at least one line of androgen receptor pathway inhibitor therapy (ARPI) and at least one line of taxane-based chemotherapy, and no more than 3 total prior lines of systemic therapy for metastatic disease.
- •Phase II: HR+/HER2- a BC with disease progression on or after an endocrine therapy in combination with a CDK4/6 inhibitor for advanced disease, with no more than 2 total lines of endocrine therapy for advanced disease, and no prior cytotoxic chemotherapy or antibody-drug conjugate therapy for advanced disease.
- •Measurable disease as determined by RECIST v1.1, with the following exceptions: aBC 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. mCRPC only: If no measurable disease is present per PCWG3 modified RECIST, then at least one metastatic lesion must be present on bone scan imaging obtained prior to C1D1.
排除标准
- •Patients with inadequate bone marrow and/or organ function.
- •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 breast cancer only: Patient is concurrently using hormone replacement therapy. Pre/perimenopausal women or men with breast cancer who are unwilling or unable to be treated with a Luteinizing Hormone-Releasing Hormone (LHRH) agonist (goserelin or leuprolide) for gonadal suppression, as per locally approved label (see Protocol Section 6.1.1).
- •Women of childbearing potential (WOCBP) who are unwilling to use highly effective contraception methods.
- •Pregnant or nursing women.
研究组 & 干预措施
GVV858, GVV858
干预措施: GVV858 (Drug)
LEUPRORELIN ACETATE, LEUPRORELIN ACETATE
干预措施: LEUPRORELIN ACETATE (Drug)
LETROZOLE
干预措施: LETROZOLE (Drug)
GOSERELIN, GOSERELIN
干预措施: GOSERELIN (Drug)
FULVESTRANT
干预措施: FULVESTRANT (Drug)
结局指标
主要结局
Phase I: Safety: Incidence and severity of dose-limiting toxicities (DLTs), adverse events (AEs) and serious adverse events (SAEs), including changes in lab values, vital signs, electrocardiograms (ECGs). Tolerability: Frequency of dose interruptions, reductions, discontinuations, dose intensity.
Phase I: Safety: Incidence and severity of dose-limiting toxicities (DLTs), adverse events (AEs) and serious adverse events (SAEs), including changes in lab values, vital signs, electrocardiograms (ECGs). Tolerability: Frequency of dose interruptions, reductions, discontinuations, dose intensity.
Phase II: Safety: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in lab values, vital signs, electrocardiograms (ECGs). Tolerability: Frequency of dose interruptions, reductions, discontinuations, dose intensity.
Phase II: Safety: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), including changes in lab values, vital signs, electrocardiograms (ECGs). Tolerability: Frequency of dose interruptions, reductions, discontinuations, dose intensity.
次要结局
- Phase II: ORR, BOR, DCR, CBR, PFS and duration of response (DOR) per investigator assessment of RECIST v1.1. Plasma concentrations of GVV858 and derived PK parameters (e.g., AUC, Tmax, and Cmax).
- Phase I: Plasma concentrations of GVV858 and derived PK parameters (e.g., AUC, Tmax, Cmax). ORR, BOR, DCR, CBR, and PFS per investigator assessment of response evaluation criteria in solid tumors (RECIST v1.1), or local PCWG3 criteria including PCWG3-modified RECIST v1.1 (prostate cancer patients only).
研究者
Novartis Pharma Arzneimittel GmbH
Scientific
Novartis Pharma AG