A Phase 1/2, First-in-Human, Safety and Efficacy Study of NUV-1511 in Adult Patients With Advanced Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 466
- 试验地点
- 8
- 主要终点
- Phase 2: Confirm the optimal NUV-1511 dose level/schedule for further development
研究概览
简要总结
NUV-1511-01 is a first-in human, open- label, Phase 1/2 to evaluate the safety and efficacy of NUV-1511 in patients with advanced solid tumors. The Phase 1 portion include patients with advanced solid tumors and is designed to determine the safety and the tolerability of doses of NUV-1511. In Phase 2, NUV-1511 will be given to determine the efficacy of patients with advanced solid tumors.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- All
- 接受健康志愿者
- 否
入选标准
- •Phase 1 Dose Escalation cohorts, Phase 1 Backfill cohorts, and Phase 2 Tumor Type-Specific cohort(s): must meet one of the following criteria:
- •HER2- metastatic breast cancer:
- •Hormone refractory hormone receptor positive metastatic breast cancer with progression on or after treatment with CDK4/6 inhibitor plus at least one line of systemic chemotherapy in the advanced setting
- •Triple negative metastatic breast cancer with progression after at one line of systemic chemotherapy in the advanced setting.
- •Patients with advanced solid tumors that progressed on or following treatment with Enhertu and/or Trodelvy per label
- •mCRPC: Histologically confirmed, metastatic castration resistant adenocarcinoma of the prostate
- •May have received up to 2 prior chemotherapies in mCRPC setting
- •Prior therapy with PARP (poly-ADP ribose polymerase) inhibitor, PLUVICTO, Radium-223, or Provenge is allowed
- •Pancreatic cancer: PDAC (pancreatic ductal adenocarcinoma) with progression on or after treatment with at least one line of systemic chemotherapy in the advanced setting.
- •PROC: Histologically or cytologically confirmed platinum-resistant high-grade serous ovarian, fallopian, or primary peritoneal cancer;
- •Phase 1 Dose Escalation cohorts, Phase 1 Backfill cohorts, and Phase 2 Tumor Type-Specific cohorts (except mCRPC; see inclusion criterion 2 above): must have measurable disease per RECIST 1.1
- •Phase 2 All Comers cohort: Patients with advanced solid tumors that have progressed during or after treatment with approved therapies or for whom there is no standard effective therapy available.
- •Adequate bone marrow and organ function.
- •Provide informed consent, which includes compliance with protocol-specified requirements and restrictions
排除标准
- •Chemotherapy, hormonal therapy (with the exception of ongoing luteinizing hormone-releasing hormone analogs in male patients and premenopausal females), radiation therapy, or biological anticancer therapy within 14 days before the first dose of study treatment
- •Treatment with an investigational agent for any indication within 14 days before the first dose of study treatment for non-myelosuppressive agent, or within 21 days or <5 half-lives before the first dose of study treatment, whichever is longer, for a myelosuppressive agent
- •Ongoing or active infection requiring systemic therapy, or an infection requiring hospitalization or intravenous therapy within 2 weeks before the first dose of study treatment
- •Resting left ventricular ejection fraction (LVEF) of <50% obtained by echocardiography or multigated acquisition scan (MUGA)
- •History of significant cardiac disease, including myocardial infarction, New York Heart Association Class II/III/IV heart failure, unstable angina, unstable cardiac arrhythmias (eg, ventricular tachycardia, ventricular fibrillation), syncope of cardiovascular etiology, or cardiac arrest:
- •Known immunosuppressive disease or active systemic autoimmune disease such as systemic lupus erythematosus, human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) infections not currently controlled by current disease-specific therapy. The following exceptions apply:
- •Major surgical procedure within 2 weeks before the first dose of study treatment, or an anticipated need for major surgery during the course of the study
- •Other cancer within 2 years before the first dose of study treatment with metastatic or local recurrence potential that could negatively impact survival and/or potentially confound tumor response assessments. Patients with a history of other cancers in the past 2 years should be discussed with the Medical Monitor.
- •Female patients who are pregnant or breastfeeding
研究组 & 干预措施
Phase 2: Tumor Type 1
Tumor type to be selected after Phase 1. Dose Schedules A and B to be further evaluated.
干预措施: NUV-1511 (Drug)
Phase 1: Schedule A
Schedule A evaluating escalating dose levels of NUV-1511
干预措施: NUV-1511 (Drug)
Phase 1: Schedule B
Schedule B evaluating escalating dose levels of NUV-1511
干预措施: NUV-1511 (Drug)
Phase 2: Tumor Type 2
Tumor type to be selected after Phase 1. Dose level and schedule to be selected after identification of the recommended phase 2 dose (RP2D) in Phase 1.
干预措施: NUV-1511 (Drug)
Phase 2: All comers
All tumor types allowed per protocol. Dose level and schedule to be selected after identification of the recommended phase 2 dose (RP2D) in Phase 1.
干预措施: NUV-1511 (Drug)
结局指标
主要结局
Phase 2: Confirm the optimal NUV-1511 dose level/schedule for further development
时间窗: Periodic efficacy assessments from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
Overall response rate per RECIST 1.1 (Composite response rate for mCRPC patients only, if enrolled in Phase 2)
Phase 1: Identify recommended dosing schedule(s) and corresponding Phase 2 dose(s) (RP2D(s))
时间窗: First 28 days of dosing (DLT evaluation period)
Number of patients with DLTs, TEAEs and SAEs and laboratory abnormalities
Phase 2: Evaluate the efficacy of NUV-1511 in advanced solid tumors and selected tumor type(s)
时间窗: From date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
Efficacy measures may include tumor assessments, as assessed by CT scans, PET/CT, whole body bone scan and MRI
Phase 2: Confirm the optimal NUV-1511 target tumor types for further development
时间窗: Periodic efficacy assessments from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first
Overall response rate per RECIST 1.1 (Composite response rate for mCRPC patients only, if enrolled in Phase 2)
Phase 1: Assess safety and tolerability of NUV-1511 in advanced solid tumors
时间窗: First 28 days of dosing (DLT evaluation period)
Number of patients with dose limiting toxicities, treatment emergent adverse events (TEAE) and serious adverse events (SAE) and laboratory abnormalities
次要结局
- Phase 1: Explore preliminary efficacy of NUV-1511(From date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first)
- Characterize the PK profile of NUV-1511(Periodic PK sample collection from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first.)
- Phase 2: Further evaluate the safety and efficacy of NUV-1511(Ongoing monitoring of safety and efficacy from date of enrollment to date of disease progression, withdrawal of consent, or initiation of subsequent anticancer treatment or up to a period of 5 years, whichever occurs first)