NCT05360680已完成1 期
A Phase 1, Open-Label, Dose Escalation and Expansion Study of CUE-102 Monotherapy in HLA-A*0201 Positive Patients With WT1 Positive Recurrent/Metastatic Cancers
适应症
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 15
- 主要终点
- Serum PK Cmax for CUE-102
研究概览
简要总结
This is a Phase 1, open-label, 2-part, multi-center study evaluating the safety, tolerability, PK, pharmacodynamics (PD), immunogenicity, and antitumor activity of CUE-102 intravenous (IV) monotherapy in HLA-A*0201 positive patients with WT1 positive recurrent/metastatic solid tumors who have failed conventional therapies.
详细描述
CUE-102 is a novel fusion protein developed for the treatment of patients with WT1-positive malignancies by selective engagement and expansion of tumor antigen-specific T cells that should allow for increased potential for anti-cancer efficacy and reduced toxicity relative to non-targeted forms of immunotherapy that result in systemic activation of the immune system.
The goal of Part A is to characterize the safety, tolerability, and biological effects of CUE-102.
The goal of Part B is to expand the safety and immune activity data at the RP2D identified in Part A, and to evaluate antitumor activity at this dose.
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
- •Ability to provide informed consent and documentation of informed consent prior to initiation of any study-related tests or procedures that are not part of standard of care for the patient's disease.
- •Age ≥18 years old
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Life expectancy ≥12 weeks
- •Measurable disease as per RECIST 1.1 and documented by CT and/or MRI.
- •All tumors must have histologically or cytologically confirmed cancer diagnosis
- •Patients must have any of the following cancers to be eligible:
- •A. Colorectal cancer
- •Histologically or cytologically documented adenocarcinoma of colon or rectum at the time of initial presentation
- •Metastatic or locally advanced/unresectable disease
- •Documented disease progression after the last administration of standard therapies or intolerance to at least 2 prior systemic treatment regimens (CUE-102 will be 3rd line therapy or greater).
- •B. Gastric cancer (including gastroesophageal junction)
- •Histologically or cytologically documented gastric cancer at the time of initial presentation
- •Metastatic or locally advanced/unresectable disease
- •Documented disease progression after last administration of standard therapies or intolerance to standard therapies. (CUE-102 will be 2nd line therapy or greater).
- •C. Pancreatic cancer
- •Histologically or cytologically documented pancreatic adenocarcinoma at the time of initial presentation
- •Patients with metastatic or locally advanced/unresectable disease.
- •Prior systemic treatment must include either a fluoropyrimidine-based or gemcitabine-based regimen in either the (neo)adjuvant or relapsed setting. (CUE-102 will be 2nd line therapy or greater).
- •D. Ovarian cancer
- •Histologically or cytologically documented ovarian cancer at the time of initial presentation
- •Metastatic or locally advanced/unresectable disease, with documented disease progression after last administration of standard therapies or intolerance to standard therapies.
- •Prior systemic treatment must include a platinum-based regimen. (CUE-102 will be 2nd line therapy or greater).
- •For patients determined to have platinum-sensitive disease, treatment with a second platinum-based combination regimen +/- bevacizumab should be considered prior to treatment with CUE-102 (CUE-102 will be 3rd line therapy or greater).
- •Patient must have HLA-A*0201 genotype as determined by genomic testing.
- •Patient must have histologically and/or cytologically proven tumor(s) that is WT1 positive.
- •Acceptable laboratory parameters.
- •Female patients of childbearing potential must agree to use acceptable contraceptive measures from the time of main study consent through 90 days after discontinuation of study drug administration.
- •Non-vasectomized male patients with partners of childbearing potential must use barrier contraception from the time of main study consent through 90 days after discontinuation of study drug.
- •Patients who have previously received an immune CPI (e.g., anti-programmed cell death ligand 1 (anti PD-L1), anti-programmed cell death 1 (anti-PD-1), anti-cytotoxic T lymphocyte-associated antigen 4 [CTLA-4]) prior to enrollment must have toxicities related to the CPI resolved to CTCAE ≤ Grade 1 or baseline (level prior to the CPI) to be eligible for enrollment. Patients who have experienced CPI-related endocrinopathies (e.g., diabetes, adrenal insufficiency) may participate if endocrinopathies are controlled (CTCAE ≤ Grade 1) with endocrinology support and appropriate repletion. Note: Patients who experienced previous hypothyroidism toxicity on a CPI are eligible to enter study regardless of CTCAE grade resolution as long as the patient is well controlled on thyroid replacement hormone.
排除标准
- •Female patients who are pregnant or plan to become pregnant during the course of the trial
- •Female patients who are breastfeeding
- •Patients with symptomatic central nervous system (CNS) metastases must have been treated, be asymptomatic, and not have any of the following at the time of enrollment:
- •Need for concurrent treatment for the CNS disease (e.g., surgery, radiation, corticosteroids >10 mg prednisone/day or equivalent)
- •Progression of CNS metastases on CT or MRI for at least 28 days after last day of prior therapy for the CNS metastases
- •Concurrent leptomeningeal disease or cord compression.
- •Has an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is permitted.
- •History of prior allogeneic bone marrow, stem-cell, or solid organ transplantation
- •Treatment with any systemic anti-neoplastic therapy, or investigational therapy within the 14 days (or 28 days, for antibody drugs), before the first dose of CUE-
- •Treatment with radiation therapy within 14 days before the first dose of CUE-102
- •Treatment with corticosteroids (> 10 mg per day prednisone or equivalent) or other immune suppressive drugs within 14 days before the first dose of CUE-
- •Steroids for topical, ophthalmic, inhaled, or nasal administration are permitted. Physiological replacement with up to a maximum dose of 5 mg equivalence of prednisone per day is permitted.
- •History of clinically significant cardiovascular disease
- •Clinically significant pulmonary compromise (e.g., requirement for supplemental oxygen)
- •Clinically significant gastrointestinal (GI) disorders
- •Patients who experienced the following immune CPI-related AEs are ineligible even if the AE resolved to ≤ Grade 1 or baseline:
- •≥ Grade 3 ocular AE
- •Changes in liver function tests that met the criteria for Hy's Law (> 3× ULN of either ALT/AST with concurrent > 2× ULN of total bilirubin (total and direct) and without alternate etiology)
- •≥ Grade 3 neurologic toxicity
- •≥ Grade 3 colitis
- •≥ Grade 3 renal toxicity
- •Evidence of active viral, bacterial, or systemic fungal infection requiring parenteral treatment within 7 days before the first dose of CUE-
- •No known history of infection or positive test for HIV, Hepatitis B or Hepatitis C, testing prior to enrollment is not required unless mandated by local authority
- •Second primary invasive malignancy that has not been in remission for > 2 years.
- •History of trauma or major surgery within 28 days before the first dose of CUE-102
- •Any serious underlying medical or psychiatric condition that would impair the ability of the patient to receive or tolerate the planned treatment at the investigational site
- •Known hypersensitivity to recombinant proteins, polysorbate 80 or any excipient contained in the drug formulation for CUE-102
- •Vaccination with any live virus vaccine within 28 days before the first dose of CUE-
- •Inactivated annual influenza vaccination is allowed.
- •Dementia or altered mental status that would preclude understanding and rendering of informed consent
- •Active or history of significant alcohol or other substance abuse within 1 year before the first dose of CUE-102
研究组 & 干预措施
CUE-102 (1mg/kg) Dose Escalation
Experimental
CUE-102 (1 mg/kg) Monotherapy IV infusion every 3 weeks for up to 2 years
干预措施: CUE-102 (Drug)
CUE-102 (2 mg/kg) Dose Escalation
Experimental
CUE-102 (2 mg/kg) Monotherapy IV infusion every 3 weeks for up to 2 years
干预措施: CUE-102 (Drug)
CUE-102 (4 mg/kg) Dose Escalation
Experimental
CUE-102 (4 mg/kg) Monotherapy IV infusion every 3 weeks for up to 2 years
干预措施: CUE-102 (Drug)
CUE-102 (8 mg/kg) Dose Escalation
Experimental
CUE-102 (8 mg/kg) Monotherapy IV infusion every 3 weeks for up to 2 years
干预措施: CUE-102 (Drug)
CUE-102 Dose Expansion at Determined RP2D
Experimental
Dose expansion of CUE-102 at determined RP2D Monotherapy IV infusion every 3 weeks for up to 2 years
干预措施: CUE-102 (Drug)
结局指标
主要结局
Serum PK Cmax for CUE-102
时间窗: Up to 2 years
Maximum serum concentration (Cmax) of CUE-102.
Serum PK AUC for CUE-102
时间窗: Up to 2 years
Area under the concentration-time curve (AUC) of CUE-102.
Serum PK T1/2 for CUE-102
时间窗: Up to 2 years
Terminal half-life (T1/2) of CUE-102.
Dose Limiting Toxicity
时间窗: 21 Days
Evaluate dose-limiting toxicities (DLTs) during the first cycle of treatment with CUE-102, and to establish a recommended Phase 2 dose (RP2D)
Maximum Tolerated Dose
时间窗: 21 Days
Evaluate maximum tolerated dose (MTD) to establish a recommended Phase 2 dose (RP2D)
次要结局
- Safety and Tolerability of CUE-102 Assessed by NCI CTCAE v5.0(Up to 2 years)
- Antitumor Duration of Response with Treatment of CUE-102(Up to 2 years)
- Immune Response Assessed by WW1 Tetramer-Positive T cell Lymphocytes(Up to 2 years)
- Antitumor Response Rate with Treatment of CUE-102(Up to 2 years)
- Immune Response Assessed by CTL Markers of Activation(Up to 2 years)
- Antitumor Clinical Benefit Rate with Treatment of CUE-102(Up to 2 years)
- Overall Survival with Treatment of CUE-102(From First CUE-102 to Date of Death)
- Progression-Free Survival with Treatment of CUE-102(Up to 2 years)
研究者
研究点 (15)
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