A Phase 1, Open-label, Dose Finding Study of NI-1801, a Bispecific Mesothelin x CD47 Engaging Antibody, in Patients With Mesothelin Expressing Solid Cancers
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 40
- 试验地点
- 7
- 主要终点
- Adverse Events (AEs)
研究概览
简要总结
Study LCB-1801-001 is an open-label, Phase 1, dose escalation (Part A) and expansion (Part B), first-in-human clinical study of NI-1801 in subjects with advanced, metastatic, or recurrent solid malignancies expressing mesothelin (MSLN).
The dose escalation part (Part A) of the study will evaluate the safety and tolerability of escalating doses of NI-1801, administered intravenously (IV) to determine the maximum tolerated dose (MTD) and non-tolerated toxic dose (NTD) of both the first dose and subsequent doses of NI-1801.
The expansion part (Part B) will further evaluate the safety and efficacy of NI-1801 administered at or below the MTD in up to 20 subjects in order to determine the recommended Phase 2 dose (RP2D).
Treatments will be administered in 28-day cycles for up to 6 months until confirmed disease progression, unacceptable toxicity, or subject/Investigator decision to withdraw. NI-1801 treatment can extend beyond 6 cycles for those patients who do not have disease progression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Adults ≥ 18 years of age at the time of signing the informed consent form.
- •Histologically or cytologically confirmed diagnosis of epithelial ovarian cancer (high-grade serous or endometroid), triple-negative breast cancer, or non-squamous non-small cell lung cancer.
- •MSLN expression with staining intensity of ≥ 2+ as per IHC in ≥ 60 % of tumor cells.
- •Patients with advanced, metastatic, or recurrent disease
- •after at least 1 prior systemic treatment for the primary malignancy and
- •who have failed treatment with, are intolerant to, or are not candidates for available therapies that are known to confer a clinical benefit to patients with these tumor entities.
- •Measurable disease according to the revised RECIST guideline version 1.1
- •Eastern Cooperative Oncology Group performance status 0-
- •Adequate organ function
- •Adequate contraception
- •Life expectancy of at least 2 months.
排除标准
- •Patient has known hypersensitivity to NI-1801 or any of the constituent compounds.
- •Radiotherapy to the target lesions within 4 weeks prior to the first NI-1801 infusion.
- •Prior anti-cancer therapy including chemotherapy, hormonal therapy, and investigational agents within 2 weeks or within ≤ 5 half-lives prior to starting NI-1801 dosing (up to a maximum of 4 weeks), whichever is longer.
- •Other investigational therapies must not be used, i.e., treatment within another clinical trial is not permitted, while the patient is on study.
- •Severe cardiac dysfunction (NYHA classification III-IV).
- •Significant hepatic dysfunction (serum bilirubin ≥ 1.5 mg/dL or AST and/or ALT ≥ 2.5 times normal level), unless related to liver metastasis.
- •Uncontrolled active systemic bacterial, viral, fungal, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment), or intravenous anti-infective treatment within 2 weeks prior to first dose of NI-
- •Patients with concomitant active malignancy, requiring ongoing systemic treatment.
- •Patients with known CNS metastases.
- •Platelet count < 100 x 10^9/L (transfusion support within 14 days before the test is not allowed).
- •Hemoglobin < 10.0 g/dL. Prior RBC transfusion is permitted.
- •ANC < 1 x 10^9/L (the use of colony stimulating factors, G-CSF or GM-CSF, within 14 days before the test is not allowed).
- •Pregnancy and lactation.
- •Significant medical diseases or conditions, including laboratory abnormalities, as assessed by the Investigators and Sponsor, that would substantially increase the risk-benefit ratio of participating in the study. This includes, but is not limited to, acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, and severely immunocompromised state, major surgery ≤ 4 weeks prior to starting NI-
- •Prior treatment with a CD47, SIRPα, or MSLN targeting agent.
- •Patients in whom acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure have not resolved to Grade ≤ 1 or returned to baseline except for alopecia (any grade), anemia, and peripheral neuropathy (for the latter, recovery to Grade ≤ 2 is acceptable).
研究组 & 干预措施
NI-1801 Single Agent
NI-1801 will be evaluated in patients with MSLN-expressing advanced, metastatic solid tumors
干预措施: Biological NI-1801 (Drug)
NI-1801 in Combination with Pembrolizumab
NI-1801 will be evaluated in patients with MSLN-expressing advanced, metastatic solid tumors in combination with anti-PD-1 antibody
干预措施: NI-1801 in combination with anti-PD1 (Pembrolizumab) (Drug)
Randomized cohort
In the randomized, open-label cohort design, the experimental arm will receive the investigational drug NI-1801 at the P2RD in combination with weekly administration of paclitaxel (80 mg/m^2) over 4-week cycles.
干预措施: NI-1801 in combination with paclitaxel (Drug)
Randomized cohort
In the randomized, open-label cohort design, the experimental arm will receive the investigational drug NI-1801 at the P2RD in combination with weekly administration of paclitaxel (80 mg/m^2) over 4-week cycles.
干预措施: Paclitaxel (Drug)
结局指标
主要结局
Adverse Events (AEs)
时间窗: Up to 12 months
Number of patients with AEs as assessed by CTCAE v5.0
Dose Limiting Toxicity (DLT)
时间窗: Up to 12 months
Is defined as any of the toxicities occurring within the DLT window (Cycle 1, Days 1 to 28) except those that are clearly and incontrovertibly due to extraneous causes.
Non-Tolerated Dose (NTD)
时间窗: Up to 12 months
Is defined as a dose level at which 2 or more of up to 6 evaluable patients in a cohort experience a DLT in the 4-week DLT window.
Maximum Tolerated Dose (MTD)
时间窗: Up to 12 months
Is defined as the last cohort below the NTD with 0 or 1 out of 6 evaluable subjects experiencing a DLT during the 4-week DLT window.
Progression Free Survival (PFS) (Randomized Cohort only)
时间窗: Up to 12 months
Defined as the time from date of randomization until Investigator-assessed progressive disease or death, whichever occurs first.
次要结局
- Pharmacokinetics - tmax(Up to 12 months)
- Overall Response Rate (ORR)(Up to 12 months)
- Disease Control Rate (DCR)(Up to 12 months)
- Best Overall Response (BOR)(Up to 12 months)
- Time to Response(Up to 12 months)
- Duration of Response(Up to 12 months)
- Progression Free Survival(Up to 12 months)
- Overall Survival(Up to 12 months)
- Pharmacokinetics - Cmax(Up to 12 months)
- Pharmacokinetics - t1/2(Up to 12 months)
- Pharmacokinetics - AUC(Up to 12 months)
- Pharmacokinetics - CL(Up to 12 months)
- Presence of anti-drug antibodies (ADA)(Up to 12 months)
- Frequency of anti-drug antibodies (ADA)(Up to 12 months)
- Functional impact of anti-drug antibodies (ADA)(Up to 12 months)
- Biomarker CA125 (Randomized cohort only)(Up to 12 months)