NCT05873686招募中1 期
A Phase 1 Clinical Study of NXP900 in Subjects With Advanced Cancers
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 140
- 试验地点
- 15
- 主要终点
- Number of patients with treatment related adverse events and/or clinical laboratory abnormalities
研究概览
简要总结
This is a multi-center, first-in-human, open label, dose escalation (Part A) and expansion (Part B) Phase 1 study in subjects with advanced solid tumors and in subjects with solid tumors with selected genetic alterations that are either direct (YES1 amplification) or dependent (Hippo Pathway alterations) targets of NXP900.
详细描述
This is a dose escalation study of NXP900 administered to patients with advanced cancers. The study will propose dose and dose schedules for future studies.
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
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion Criteria:
- •Provide written informed consent.
- •18 years old or older.
- •Advanced, metastatic, and/or progressive solid tumors for whom there is no authorized or effective therapy available, or for whom such therapies are considered inappropriate by the Investigator.
- •Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
排除标准
- •Subjects with known human epidermal growth factor receptor 2 (HER2+) overexpressing malignancies.
- •Radiotherapy (except for palliative reasons), endocrine therapy, chemotherapy, or investigational agent within 28 days, (42 days for nitrosoureas, mitomycin-C) of first dose of NXP
- •Subjects can continue to receive bisphosphonates due to metastatic bone disease or GnRH agonists if they have prostate cancer.
- •Ongoing toxic manifestations of previous treatments > Grade 2 with the exception of alopecia and neuropathy.
- •Subjects with treated brain metastases with evidence of progression within 28 days after central nervous system (CNS)-directed treatment, as ascertained by clinical examination and brain imaging (magnetic resonance imaging [MRI] or computed tomography [CT] scan) during the Screening period.
- •Female subjects who can become pregnant (or are already pregnant or lactating), unless they have a negative serum pregnancy test before enrollment and agree to use at least one highly effective form of contraception .
- •Male subjects with partners of childbearing potential, unless they agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide).
- •Major surgery from which the subject has not yet recovered.
- •Inclusion Criteria:
- •Provide written informed consent.
- •18 years old or older.
- •Advanced, metastatic, and/or progressive solid tumors with pathogenic molecular alterations:
- •Non-small cell lung cancer (adenocarcinoma); YES1, TYMS amplification or FAT1 pathogenic mutation
- •Non-small cell lung cancer (squamous cell carcinoma); YES1, TYMS amplification or FAT1 pathogenic mutation
- •Renal cancer; NF2 pathogenic mutation
- •Mesothelioma; NF2 pathogenic mutation
- •Other solid tumors with a NF2, FAT1 or LATS1 pathogenic gene mutation or TYMS, YAP1, YES1, or TAZ1 gene amplification, or cholangiocarcinoma with IDH1 or IDH2 mutations.
- •Must have received 1-3 prior therapies appropriate for their tumor type and stage of disease
- •Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (or mRECIST 1.1 for subjects with pleural mesothelioma).
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Exclusion Criteria:
- •Subjects with the following combination of cancer type and pathogenic molecular alterations are excluded:
- •Subjects with colorectal cancer, glioma, melanoma, or anaplastic thyroid conditions with BRAF mutations.
- •Subjects with NSCLC with BRAF or EGFR mutations or HER2 overexpression.
- •Subjects with breast cancer, gastric cancer, esophageal junction adenocarcinoma or biliary cancer with HER2 alterations,
- •Subjects with anal, penile, cervical or head and neck cancers with a prior history of human papilloma virus (HPV) infection.
- •Radiotherapy (except for palliative reasons), endocrine therapy, chemotherapy, or investigational agent within 28 days (42 days for nitrosoureas, mitomycin-C) prior to first dose of NXP
- •Subjects can continue to receive bisphosphonates due to metastatic bone disease or GnRH agonists if they have prostate cancer.
- •Ongoing toxic manifestations of previous treatments > Grade 2 with the exception of alopecia and neuropathy.
- •Female subjects who can become pregnant (or are already pregnant or lactating), unless they have a negative serum pregnancy test before enrollment and agree to use at least one highly effective form of contraception .
- •Male subjects with partners of childbearing potential, unless they agree to take measures not to father children by using a barrier method of contraception (condom plus spermicide).
- •Major surgery from which the subject has not yet recovered.
研究组 & 干预措施
Dose Escalation (Part A)
Experimental
Escalating doses of NXP900 are planned with a starting dose level of 20 mg once per day.
干预措施: NXP900 (Drug)
Dose Expansion (Part B)
Experimental
Participants will receive the selected dose of NXP900
干预措施: NXP900 (Drug)
结局指标
主要结局
Number of patients with treatment related adverse events and/or clinical laboratory abnormalities
时间窗: Up to 30 days post treatment
Part A: Number of patients who experience Dose Limiting Toxicities (DLT) as defined in the protocol
时间窗: Day 28
Part B: Duration of Response (DoR)
时间窗: Up to 24 months
Confirmed CR or PR from the first documented response to the date of documented disease progression or death.
Part B: Disease Control Rate (DCR)
时间窗: Up to 24 months
The proportion of patients with stable disease (SD), partial response (PR), or complete response (CR).
Part B: Objective response rate (ORR)
时间窗: Up to 24 months
Best response of complete response (CR) or partial response (PR) per RECIST 1.1 (or mRECIST 1.1 for subjects with pleural mesothelioma).
次要结局
- Area under the concentration-time curve (AUC) of NXP900(Up to 24 months)
- Maximum observed concentration (Cmax) of NXP900(Up to 24 months)
- Time to peak concentration (Tmax) of NXP900(Up to 24 months)
- Half-life (T1/2) of NXP900(Up to 24 months)
- Apparent volume of distribution at steady state (Vss/F) of NXP900(Up to 24 months)
- Apparent plasma clearance at steady state (Clss/F) of NXP900(Up to 24 months)
研究者
研究点 (15)
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