Phase 1/2 Study of RTX-240 Monotherapy and in Combination With Pembrolizumab
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 69
- 试验地点
- 11
- 主要终点
- Safety Assessment: Measured by incidence of Treatment Emergent Adverse Events (TEAEs)
研究概览
简要总结
Open label, multicenter, multidose, first-in-human Phase 1/2 study of RTX-240 monotherapy or in combination of pembrolizumab for the treatment of patients with (1) relapsed/refractory R/R or locally advanced solid tumors (Phase 1/2) or (2) R/R Acute Myeloid Leukemia (AML) (Phase 1 only).
详细描述
This is a Phase 1/2, open label, multicenter, multidose, first-in-human (FIH) dose escalation and expansion study to determine the safety and tolerability, recommended phase 2 dose and optimal dosing interval, pharmacology, and antitumor activity of RTX-240 in adult patients with relapsed/refractory (R/R) or locally advanced solid tumors (Phase 1/2) or R/R acute myeloid leukemia (Phase 1 only), and RTX-240 in combination with pembrolizumab in adult patients with R/R or locally advanced solid tumors (Phase 1 only). RTX-240 is a cellular therapy that co-expresses 4-1BBL and IL-15TP, a fusion of IL-15 and IL-15 receptor alpha, with the goal of stimulating the innate and adaptive immune systems for the treatment of cancer. The study includes a monotherapy dose escalation phase (Phase 1) followed by an expansion phase (Phase 2) in specified tumor types.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Signed written informed consent obtained prior to study procedures
- •Patients ≥18 years with an ECOG 0 or 1 (Parts 1, 2 and 4) or 0-2 (Part 3).
- •Relapsed/Refractory (R/R) or locally advanced, unresectable solid tumor for which no standard therapy exists (Parts 1, 2 and 4), or for which the patient is ineligible or has declined standard therapy or R/R, cytologically confirmed AML (Part 3).
- •Disease must be measurable per Response Evaluation Criteria
- •The shorter of 28 days or 5 half-lives must have elapsed since the completion of prior therapy, before initiation of study treatment.
- •Adequate Organ Function and Blood Cell Counts (Parts 1, 2, and 4) as defined by the protocol:
- •GFR ≥ 50 mL/min/1.73,
- •AST and ALT ≤ 3 × the ULN and total bilirubin ≤ 1.5 × ULN, in the absence of cancer within the liver
- •Or AST and ALT ≤ 5 × ULN and total bilirubin ≤ 3 × ULN, in the setting of primary or metastatic liver tumors.
- •ANC ≥ 1 × 10^3/μL without myeloid growth factor support for at least one week prior to enrollment
- •Platelet count ≥ 75 × 10^3/μL
- •Hemoglobin should be ≥ 9 g/dL without red blood cell transfusion for at least one week
- •Patients must have LVEF ≥ 45%
- •Patients enrolling into Part 2 of the study must be diagnosed with NSCLC, RCC, or anal cancers
- •Patients enrolling into Part 4 must be diagnosed with NSCLC or RCC
- •Patients enrolling into either Part 2 or 4 must have 2 or fewer prior treatment regimens. If patient received a prior PD-1/PD-L1-containing regimen, a prior response is required.
排除标准
- •Primary central nervous system (CNS) malignancy or CNS involvement, unless asymptomatic, previously treated, and stable without steroids (Parts 1, 2 and 4) or known CNS leukemia (Part 3).
- •Known hypersensitivity to any component of study treatment or excipients.
- •Positive antibody screen using institution's standard type and screen test.
- •Clinically significant, active and uncontrolled infection, including human immunodeficiency virus (HIV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV).
- •Clinically significant coagulopathy, uncontrolled hypertension or autoimmune hemolytic anemia
- •Class III or IV cardiomyopathy per the New York Heart Association criteria
- •Leukemic blast count ≥ 25 x 10^3/µL (Part 3)
- •Concomitant conditions requiring active immunosuppression
- •History of clinically significant Grade 3 or higher immune related Adverse Event (irAE)
- •Prior malignancy within the past 3 years, with protocol specified exceptions
- •History of severe hypersensitivity to a PD-1/PD-L1 blocking Ab unless previously rechallenged successfully (Part 4)
- •Current noninfectious pneumonitis or a history of radiation pneumonitis or pneumonitis that required steroids, or Grade 2 or greater immune related pneumonitis, hepatitis, hypophysitis, or other endocrinopathy (Part 4)
研究组 & 干预措施
Part 1: RTX-240 Dose Escalation
Phase 1: RTX-240 monotherapy dose escalation in Solid Tumors
干预措施: RTX-240 (Drug)
Part 2: RTX-240 Solid Tumor Expansion
Phase 2: RTX-240 monotherapy dose expansion in Non-small Cell Lung Cancer (NSCLC), Renal Cell Carcinoma (RCC), and anal cancers
干预措施: RTX-240 (Drug)
Part 3: RTX-240 Dose Escalation
Phase 1: RTX-240 monotherapy dose escalation in AML
干预措施: RTX-240 (Drug)
Part 4: RTX-240 Plus Pembrolizumab Dose Escalation
Phase 1: RTX-240 dose escalation in combination with Pembrolizumab in Solid Tumors
干预措施: RTX-240 (Drug)
Part 4: RTX-240 Plus Pembrolizumab Dose Escalation
Phase 1: RTX-240 dose escalation in combination with Pembrolizumab in Solid Tumors
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Safety Assessment: Measured by incidence of Treatment Emergent Adverse Events (TEAEs)
时间窗: Up to 38 months
Dose limiting toxicities (DLTs) of study treatment as determined by incidence and severity of adverse events (AEs)
时间窗: Up to 38 months
次要结局
- Anti-tumor activity of study treatment measured by time to progression (TTP)(Up to 38 months)
- PK of study treatment as measured by detection of the number of cells positive for both 4-1BBL and IL-15 using flow cytometry.(Assessed From the 1st dose of RTX-240 until 30 days after last of study treatment)
- Determination of the Immunogenicity of study treatment Measured by the incidence of antibodies to RTX-240(Assessed From the 1st dose of RTX-240 until 30 days after last of study treatment)
- Anti-tumor activity of study treatment measured by progression free survival (PFS)(Up to 38 months)
- Anti-tumor activity of study treatment measured by time to response (TTR).(Up to 38 months)
- Anti-tumor activity of study treatment measured by overall survival (OS)(Up to 38 months)
- Anti-tumor activity of study treatment measured by duration of response (DoR)(Up to 38 months)
- Anti-tumor activity of study treatment measured by clinical benefit rate (CBR) (% of patients who achieve CR, PR or stable disease [SD])(Up to 38 months)
- Anti-Tumor activity of study treatment Measured by Objective Response Rate (ORR)(Up to 38 months)
- Proportion of AML patients with CR, CR with incomplete recovery (CRi), morphologic leukemia-free state, or PR(Up to 38 months)