A Phase 1/1b, Multicenter, Open-label, Dose Escalation and Expansion Study Evaluating the Safety, Pharmacodynamics, and Pharmacokinetics of ODC-IL2 Administered Via Intravenous Infusion in Adult Patients With Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Incidence of Dose Limiting Toxicities (DLTs)
研究概览
简要总结
This is a first-in-human, Phase I, multicenter, open-label, dose escalation study with dose expansion to evaluate the safety and antitumor activity of ODC-IL2 in patients with advanced or metastatic solid tumors. ODC-IL2 is a conditionally activated IL-2 prodrug and will be administered as a single agent via intravenous infusion on Days 1 and 15 of a 28-day cycle. Up to approximately 50 patients will be enrolled in this study.
详细描述
This is a first-in-human, Phase I, multicenter, open-label, dose-escalation and expansion study evaluating the safety, pharmacodynamics, pharmacokinetics and preliminary antitumor activity of ODC-IL2 for the treatment of patients with advanced or metastatic solid tumors. Part 1 of the study is dose escalation of ODC-IL2 and up to 18 to 30 patients (for up to 10 dose levels) or more will be enrolled in this portion of the study (depending on the number of dose escalation cohorts and patients per cohort required). Once the MTD or RDR has been established in dose escalation, a Part 2 expansion will begin. The dose-expansion cohort at a single dose level will enroll approximately 20 patients with advanced solid tumors to further evaluate safety and assess for signals of antitumor activity. The objective of the dose-escalation and expansion is to define, with a limited number of patients, the safety and toxicity characteristics of ODC-IL2. The study drug ODC-IL2 is a conditionally activated IL-2 prodrug and will be administered as a single agent by IV infusion over a 60-minute period on Days 1 and 15 of the treatment cycle. A treatment cycle is defined as 28 days.
This trial will enroll adult patients with advanced or metastatic solid tumors that have not responded to or have recurred following treatment with available therapies. Up to approximately 50 evaluable patients may be enrolled in this study across the dose-escalation and dose-expansion cohorts. Enrollment in this study is anticipated to be 15 to 18 months.
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
- •Each patient must meet all the following criteria to participate in the study:
- •Histologically or cytologically confirmed advanced or metastatic solid tumors, for which no other standard treatment is available or appropriate, or for which the Trutino Biosciences Protocol #: TRT-ODC-IL2-001 Version: 1.0 Date: 20 September 2024 standard of care is refused by the patient due to tolerability or the Investigator believes the patient will not tolerate standard-of-care therapy
- •Advanced or metastatic tumors measurable per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria;
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
- •Life expectancy of at least 3 months;
- •Age ≥ 18 years;
- •Signed, written Institutional Review Board (IRB)/Ethics Committee (EC)-approved informed consent
- •Acceptable liver function:
- •Bilirubin ≤ 1.5 times upper limit of normal (ULN) or ≤ 5 × institutional ULN for patients who have serum bilirubin increases due to underlying Gilbert's Syndrome (familial benign unconjugated hyperbilirubinemia).
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤ 2.5 x ULN (if liver metastases are present, then ≤ 5 x ULN is allowed)
- •Acceptable renal function:
- •Calculated creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault equation.
- •Acceptable hematologic status:
- •Absolute neutrophil count ≥ 1500 cells/mm3
- •Platelet count ≥ 75,000 (plt/mm3)
- •Hemoglobin ≥ 9 g/dL
- •A negative serum pregnancy test (if a woman of childbearing potential);
- •Women of childbearing potential (WOCBP) and men with WOCBP partners must agree to use adequate contraception (hormonal method of birth control; intrauterine devices or abstinence) prior to study entry, for the duration of study participation and for 4 months after the last dose of study drug. Should a female trial participant or a female partner of a male trial participant become pregnant or suspect she is pregnant during the study, the Investigator must be informed immediately.
排除标准
- •New York Heart Association Class III or IV, cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on electrocardiogram (ECG)
- •Have a corrected QT interval (using Fridericia's correction formula) (QTcF) of > 470 msec
- •Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
- •Known active brain metastases; patients with previously treated, clinically stable, radiologically stable brain metastases (without evidence of progression in 4 weeks) and without the requirement for treatment with corticosteroids in prior 3 weeks may be considered for enrollment after discussion with the Medical Monitor
- •History of prior organ transplant
- •Conditions requiring systemic treatment with corticosteroids or any other form of immunosuppressive therapy within 7 days prior to start of study drug.
- •History of autoimmune diseases requiring systemic immunosuppressive therapy in the last 2 years
- •Pregnant or nursing women.
- •Treatment with radiation therapy, major surgery, chemotherapy, or investigational therapy within 4 weeks prior to study entry (6 weeks for nitrosoureas or mitomycin C). Radiation for palliation of pain is allowed within 1 week prior to study entry, but the lesion should not be selected as a target lesion for RECIST analysis.
- •Unwillingness or inability to comply with procedures required in this protocol
- •Known active infection with human immunodeficiency virus (HIV), human T-cell leukemia virus, type 1 (HTLV-1), hepatitis B virus (HBV), or hepatitis C virus (HCV)
- •Patients with a history of hepatitis B or C are allowed if HBV DNA or HCV RNA are undetectable
- •Active infection with HIV and CD4+ T-cell count <350/μL. Patients not on established anti-retroviral therapy for at least 4 weeks and having a detectable HIV viral load
- •Serious uncontrolled nonmalignant disease (e.g., renal failure, liver failure, or other conditions) that could compromise protocol objectives in the opinion of the investigator and/or the sponsor
- •Prior treatment with an IL-2 targeted treatment, unless given as a part of a tumor infiltrating lymphocyte treatment combination;
- •Known sensitivity to IL-2 or any of the excipients in ODC-IL2;
- •Active treatment with heparin or heparin-related therapies, unless the patient can be transitioned to a non-heparin treatment for the clinical condition with an adequate washout prior to enrollment in the study.
研究组 & 干预措施
ODC-IL2 monotherapy dose escalation
All patients will receive ODC-IL2 as a single agent infused IV over 60 minutes on Days 1 and 15 of a 28 day cycle.
干预措施: ODC-IL2 (Drug)
ODC-IL2 monotherapy dose expansion
All patients will receive ODC-IL2 as a single agent infused IV over 60 minutes on Days 1 and 15 of a 28 day cycle.
干预措施: ODC-IL2 (Drug)
结局指标
主要结局
Incidence of Dose Limiting Toxicities (DLTs)
时间窗: 28 days
Incidence of Treatment-Emergent Adverse Events (TEAEs)
时间窗: From the first administration of study drug, throughout the course of the study, and for 90 days after the last dose of study drug
All AEs will be assessed per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and American Society for Transplantation and Cellular Therapy (ASTCT) Consensus Grading for cytokine release syndrome (CRS) based on investigator assessment.
Incidence of changes in clinical laboratory abnormalities
时间窗: From the first administration of study drug, throughout the course of the study, and for 90 days after the last dose of study drug
次要结局
- Serum concentrations of ODC-IL2, free IL-2 and drug backbone following release of IL-2(24 months)
- Investigator-assessed Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1(24 months)
- Disease control rate (DCR) by RECIST 1.1(through 6 months after start of treatment)
- Duration of response (DoR) by RECIST 1.1(24 months)
- Progression-free survival (PFS) by RECIST 1.1(24 months)
- To assess tumor biopsies for pharmacodynamic markers of target engagement and immune pathway activation(24 months)