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
概览
- 阶段
- 1 期
- 干预措施
- CUE-102
- 疾病 / 适应症
- Colorectal Cancer
- 发起方
- Cue Biopharma
- 入组人数
- 42
- 试验地点
- 15
- 主要终点
- Serum PK Cmax for CUE-102
- 状态
- 已完成
- 最后更新
- 3个月前
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.
研究者
入排标准
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
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
研究组 & 干预措施
CUE-102 (1mg/kg) Dose Escalation
CUE-102 (1 mg/kg) Monotherapy IV infusion every 3 weeks for up to 2 years
干预措施: CUE-102
CUE-102 (2 mg/kg) Dose Escalation
CUE-102 (2 mg/kg) Monotherapy IV infusion every 3 weeks for up to 2 years
干预措施: CUE-102
CUE-102 (4 mg/kg) Dose Escalation
CUE-102 (4 mg/kg) Monotherapy IV infusion every 3 weeks for up to 2 years
干预措施: CUE-102
CUE-102 (8 mg/kg) Dose Escalation
CUE-102 (8 mg/kg) Monotherapy IV infusion every 3 weeks for up to 2 years
干预措施: CUE-102
CUE-102 Dose Expansion at Determined RP2D
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
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)