A Phase 1, Multicenter, Open-Label, Dose Escalation and Expansion Study to Evaluate the Safety, Tolerability, PK/PD, and Clinical Activity of Intravenously Administered KT-413 in Adult Patients with Relapsed or Refractory B-cell NHL
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 7
- 试验地点
- 8
- 主要终点
- To establish the Maximum Tolerated Dose (MTD)
研究概览
简要总结
This Phase 1a/1b study will evaluate the safety, tolerability and the pharmacokinetics/ pharmacodynamics (PK/ PD) of KT-413 in patients with R/R NHL. The Phase 1a stage of the study will explore escalating doses of single-agent KT-413. The Phase 1b stage will be split into 2 expansion cohorts to further characterize the safety, tolerability and the pharmacokinetics/ pharmacodynamics (PK/ PD) of KT-413 in MYD88 mutant and MYD88 wild-type R/R DLBCL.
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
- •Phase 1a Only:
- •Histologically confirmed diagnosis of B-cell NHL according to the 2016 World Health Organization (WHO) classification. Diffuse large B-cell lymphoma (DLBCL) includes: DLBCL not otherwise specified (NOS) with or without MYC and BCL2 and/or BCL6 rearrangements; Epstein-Barr virus (EBV) positive DLBCL, NOS; human herpesvirus 8 (HHV8) positive DLBCL, NOS; DLBCL associated with chronic inflammation; and Primary cutaneous DLBCL, leg type. Patients with indolent lymphoma are eligible if they meet criteria for systemic treatment.
- •Clinicopathological diagnosis of Waldenström's Macroglobulinemia (WM) based on the consensus panel criteria from the Second International Workshop on WM
- •Histologically/cytologically confirmed relapsed/refractory Primary Central Nervous System Lymphoma (PCNSL) by cerebrospinal fluid (CSF) or biopsy. PCNSL patients are considered eligible if the Investigator believes that there is no other reasonable treatment alternative.
- •Note: Patients with HIV-associated PCNSL are not eligible.
- •Note: Patients with secondary CNS metastases are eligible assuming they meet other study criteria. Patients with secondary CNS metastases include those who have synchronous systemic and CNS involvement or those who have been previously treated and relapsed with isolated CNS involvement.
- •Phase 1b Only: Histologically confirmed diagnosis of DLBCL according to the 2016 WHO classification including: DLBCL not otherwise specified (NOS) with or without MYC and BCL2 and/or BCL6 rearrangements; Epstein-Barr virus (EBV) positive DLBCL, NOS; HHV8+ DLBCL, NOS; DLBCL associated with chronic inflammation; and Primary cutaneous DLBCL, leg type.
- •Disease relapsed and/or refractory to at least 2 accepted standard systemic regimens for all indications except PCNSL. For PCNSL, patients must be relapsed and/or refractory to at least 1 prior regimen.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2 at Screening.
- •Adequate organ and bone marrow function, in the absence of growth factors
- •Patients of child-bearing potential must use adequate contraceptive measures to avoid pregnancy for the duration of the study as defined in the protocol
排除标准
- •Infection with hepatitis B (HBV), hepatitis C (HCV), or active viral infection with human immunodeficiency virus (HIV).
- •Radiation treatment within 4 weeks prior to first dose of study drug, unless the tumor site continues to increase in size after the patient has completed radiotherapy treatment.
- •Major surgery requiring general anesthesia within 4 weeks prior to first dose of study drug, unless the tumor site continues to increase in size after the patient has completed radiotherapy treatment.
- •Ongoing unstable cardiovascular function including history of myocardial infarction within 3 months of planned start of study drug.
- •Patient has not recovered from any clinically significant AEs of previous treatments to pre-treatment baseline or Grade 1 prior to first dose of study drug.
研究组 & 干预措施
Phase 1b Dose Expansion MYD88MT
KT-413 given at the RP2D identified in Phase 1a Dose Escalation in patients with MYD88 mutant DLBCL.
干预措施: KT-413 (Drug)
Phase 1b Dose Expansion MYD88WT
KT-413 given at the RP2D identified in Phase 1a Dose Escalation in patients with MYD88 wild type DLBCL.
干预措施: KT-413 (Drug)
Phase 1a Dose Escalation
干预措施: KT-413 (Drug)
结局指标
主要结局
To establish the Maximum Tolerated Dose (MTD)
时间窗: Within first 3 weeks of treatment
Phase 1a
Number of Participants with protocol specified Dose Limiting Toxicities (DLTs)
时间窗: Within first 3 weeks of treatment
Phase 1a
Clinical Laboratory Abnormalities
时间窗: Clinical laboratory abnormalities will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy
Incidence and severity of clinical laboratory abnormalities in serum chemistry, hematology, coagulation parameters, and urinalysis tests as assessed by CTCAE v5.0 (Phase 1a/1b)
Dose recommended for future studies
时间窗: Within first 3 weeks of treatment
Phase 1a/1b
ECG Parameters
时间窗: ECG Parameters will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy
Changes in the ECG parameters, including heart rate and measures PR, QRS, QT, and QTc intervals as assessed by CTCAE v5.0 Phase 1a/1b
Adverse Event Parameters
时间窗: Adverse Event Parameters will be assessed from the time ICF signature through 30 days post dose or prior to start of a new anticancer therapy
Incidence and severity of adverse events as assessed by CTCAE v5.0 (Phase 1a/1b)
次要结局
- Maximum Plasma Concentration of KT-413 (Cmax)(Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days))
- Evidence of clinical activity of KT-413 as determined by Objective Response Rate (ORR)(From date of baseline scan until the date of first documented progression or date of death from any cause, whichever came first, about 18 months)
- Progression-free survival (PFS) as assessed by the Investigator(From time of entry on study through progression, up to 18 months)
- Half-life of KT-413 [if data permits (T1/2)](Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days))
- Area under the plasma concentration versus time curve for KT-413 from time zero to last quantifiable time point (AUC0-t)(Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days))
- Time of maximum plasma concentration of KT-413 (Tmax)(Blood samples for PK analysis collected at multiple visits during cycle 1 and cycle 2 (each cycle is 21 days))
- Overall Survival (OS) as assessed by the investigator(From time of entry on study through death or date last known alive at end of follow-up, up to 18 months)
- Amount of KT-413 excreted in urine from time zero to last collected timepoint (Ae0-t)(Urine samples for PK analysis collected during the first cycle (21 day cycle))
- Duration of Response (DOR) as assessed by the Investigator(From date of baseline scan until the date of first documented progression or date of death from any cause, whichever came first, about 18 months)
- Disease Control Rate (DCR) as assessed by the investigator(From date of baseline scan until the date of first documented progression or date of death from any cause, whichever came first, about 18 months)