A Phase 1, Open-label, Multi-center, Dose Escalation and Dose Expansion Study of NKTR-255 in Relapsed or Refractory Hematological Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 13
- 主要终点
- Evaluate the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of NKTR-255 as a single agent
研究概览
简要总结
Patients will receive intravenous (IV) NKTR-255 in 21 or 28 day treatment cycles. During the Part 1 dose escalation portion of the trial, patients will either receive NKTR-255 as monotherapy, NKTR-255 administered as a doublet with daratumumab subcutaneous (DARZALEX FASPRO TM), or NKTR-255 administered as a doublet with rituximab. After determination of the recommended Phase 2 dose (RP2D) of NKTR-255, NKTR-255 will be evaluated in Part 2. During the Part 2 dose expansion portion of the trial, patients will either receive NKTR-255 as monotherapy, NKTR-255 administered as a doublet with daratumumab subcutaneous (DARZALEX FASPRO TM), or NKTR-255 administered as a doublet with rituximab.
This is a Phase 1 study to evaluate safety and tolerability of NKTR-255 alone and in combination with daratumumab or rituximab.
详细描述
NKTR-255 is a cytokine that is designed to regulate T and natural killer cell activation, proliferation and promote their anti-tumor effects.
This is a Phase 1, open-label, multi-center, dose escalation, dose expansion, safety follow-up, and survival follow-up of NKTR-255 as a single agent and NKTR-255 in combination with DARZALEX FASPRO TM or rituximab. Study treatment is defined as any investigational treatment(s) or marketed product(s), intended to be administered to a study patient according to the study enrollment.
Part 1 will enroll relapsed/refractory multiple myeloma (MM) and Non-Hodgkin's Lymphoma (NHL) patients. In Part 2, Cohort A will enroll NHL patients who have progressed on a chimeric antigen receptor T-cell (CAR-T) product, Cohort B will enroll MM patients who previously received daratumumab and other anti-CD38 therapies to receive NKTR-255 alone and/or in combination with daratumumab, and Cohort C will enroll indolent Non-Hodgkin's Lymphoma (iNHL) patients who previously received rituximab and other therapies to receive NKTR-255 alone and/or in combination with rituximab.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have relapsed or refractory MM or NHL with no available therapies that would confer clinical benefit for their primary disease.
- •For MM patients, measurable relapsed or refractory MM as defined by the IMWG Criteria (Kumar, 2016) following treatment with at least 3 lines of therapy with no other available treatment that would confer benefit.
- •For NHL patients, measurable or detectable disease according to International Myeloma Working Group (IMWG) and the Lugano Classification. Extranodal NHL disease that is measurable by fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging only is allowed.
- •Estimated glomerular filtration rate (eGFR) ≥ 40 mL/min/1.73 m
- •Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 2
- •Patient has the following laboratory test results during Screening:
- •Absolute neutrophil count (ANC) or absolute granulocyte count (AGC) ≥ 1000/µL
- •Platelets ≥ 30,000/µL
- •Hemoglobin ≥ 8g/dL
- •Absolute lymphocytes ≥ 500/µL
- •Leukocytes ≥ 3000/µL
- •Patients are eligible who also meet all the following criteria in these cohorts of Part 2:
- •NKTR-255 Monotherapy NHL Group Only:
- •Patients with NHL who received a commercially approved CD19 CAR-T product and had PD. The first dose of NKTR-255 will be administered within 30 days of the PD.
- •NKTR-255 with Daratumumab MM Group Only :
- •Patients with MM must have had previous exposure to proteasome inhibitor, immunomodulatory agent (IMiD), and anti-CD38 therapy.
- •Patients who previously received daratumumab or other anti-CD38 therapies must have at least 3 months washout.
- •NKTR-255 with Rituximab Group iNHL Group Only:
- •Patients with relapsed or refractory iNHL who previously progressed during or following 1 or more prior systemic rituximab-containing (or another treatment with an anti-CD20 antibody-containing) regimens for lymphoma.
排除标准
- •Patients who have an active, known, or suspected autoimmune disease.
- •Any treatment-related neurotoxicity or cytokine release syndrome (CRS) prior to enrollment into the study should return to baseline before NKTR-255 treatment.
- •Active central nervous system (CNS) involvement with NHL.
- •Patients who have been previously treated with prior interleukin-2 or interleukin-
- •Patients who received daratumumab or other anti-CD38 therapies previously must have 3 months washout.
- •NOTE: Other protocol defined Inclusion/Exclusion criteria may apply
研究组 & 干预措施
Dose Escalation
Evaluation of NKTR-255 as:
- Monotherapy
- In combination with daratumumab
- In combination with rituximab
This phase will help to determine the RP2D of NKTR-255
干预措施: NKTR-255 (Drug)
Dose Escalation
Evaluation of NKTR-255 as:
- Monotherapy
- In combination with daratumumab
- In combination with rituximab
This phase will help to determine the RP2D of NKTR-255
干预措施: Rituximab (Drug)
Dose Escalation
Evaluation of NKTR-255 as:
- Monotherapy
- In combination with daratumumab
- In combination with rituximab
This phase will help to determine the RP2D of NKTR-255
干预措施: Daratumumab (Drug)
Dose Expansion Cohort A
Evaluation of RP2D of NKTR-255 as monotherapy in patients with NHL relapsed after CAR-T
干预措施: NKTR-255 (Drug)
Dose Expansion Cohort B
Evaluation of RP2D of NKTR-255 as monotherapy and in combination with SC daratumumab in patients with R/R MM
干预措施: NKTR-255 (Drug)
Dose Expansion Cohort B
Evaluation of RP2D of NKTR-255 as monotherapy and in combination with SC daratumumab in patients with R/R MM
干预措施: Daratumumab (Drug)
Dose Expansion Cohort C
Evaluation of RP2D of NKTR-255 as monotherapy and in combination with rituximab in patients with R/R iNHL
干预措施: NKTR-255 Q21 (Drug)
Dose Expansion Cohort C
Evaluation of RP2D of NKTR-255 as monotherapy and in combination with rituximab in patients with R/R iNHL
干预措施: Rituximab (Drug)
结局指标
主要结局
Evaluate the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of NKTR-255 as a single agent
时间窗: Through study completion, an expected average of 6 months
Evaluate the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of NKTR-255 in combination with daratumumab SC
时间窗: Through study completion, an expected average of 1 year
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 as a single agent
时间窗: Through study completion, an expected average of 6 months
Safety and tolerability of NKTR-255 as evaluated by incidence of Dose Limiting Toxicities (DLTs), drug-related Adverse Events (AEs), Serious Adverse Events (SAEs), AEs leading to discontinuation, deaths, clinical laboratory abnormalities per CTCAE v5.
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 with daratumumab SC
时间窗: Through study completion, an expected average of 1 year
Safety and tolerability of NKTR-255 in combination with daratumumab as evaluated by incidence of drug-related AEs, SAEs, AEs leading to discontinuation, deaths, clinical laboratory abnormalities per CTCAE v5
Incidence of Treatment-Emergent Adverse Events and Serious Adverse Events of NKTR-255 with rituximab
时间窗: Through study completion, an expected average of 1 year
Safety and tolerability of NKTR-255 in combination with rituximab as evaluated by incidence of drug-related AEs, SAEs, AEs leading to discontinuation, deaths, clinical laboratory abnormalities per CTCAE v5
Evaluate the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of NKTR-255 in combination with rituximab
时间窗: Through study completion, an expected average of 1 year
次要结局
未报告次要终点