An Open-Label, Single-Arm, Multicenter Phase I Clinical Study to Evaluate the Safety and Preliminary Efficacy of NK042 Cell Injection (Universal NKR+NK) in Advanced Solid Tumors
概览
- 阶段
- 1 期
- 干预措施
- NK042
- 疾病 / 适应症
- Advanced Solid Tumors
- 发起方
- Shanghai NK Cell Technology Co., LTD
- 入组人数
- 76
- 试验地点
- 2
- 主要终点
- Incidence of Adverse events (AEs) and Serious Adverse Events (SAEs)
- 状态
- 招募中
- 最后更新
- 26天前
概览
简要总结
This is a single-arm, open-label, multi-center phase 1 clinical study designed to evaluate the safety and preliminary efficacy of NK042 cell injection in patients with advanced solid tumors.
详细描述
This study is divided into two phases: Phase Ia and Phase Ib. Dose-Escalation and Expansion: * Phase Ia: This dose-escalation phase involves both single-dose and multiple-dose administrations of NK042 in patients with advanced solid tumors. * Phase Ib: This multiple-dose cohort-expansion phase will focus on solid tumor indications that demonstrated preliminary efficacy in Phase Ia.
研究者
入排标准
入选标准
- •Voluntary signing of a written informed consent form.
- •Age between 18 and 70 years.
- •Histologically or cytologically confirmed locally advanced or metastatic solid tumor patients who are not amenable to surgical resection, with no standard treatment options, or who have relapsed or progressed after standard treatment, or are resistant or intolerant to standard treatment.
- •At least one assessable tumor lesion according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0-
- •Expected survival ≥12 weeks.
- •Must have adequate bone marrow, liver, and renal function.
排除标准
- •Insufficient washout period for prior anti-tumor treatments before the first dose, including chemotherapy, targeted therapy, antibody therapy, and radiotherapy.
- •Participation in another clinical trial and use of investigational drugs within 28 days before the first dose.
- •Requirement for anticoagulation therapy.
- •Symptomatic brain parenchymal metastases with less than 4 weeks of stability after treatment.
- •Active pulmonary diseases, including but not limited to interstitial lung disease, pneumonitis.
- •Uncontrolled active infections.
- •Uncontrollable massive pleural effusion, ascites, or pericardial effusion.
- •Previous receipt of other cellular therapies.
- •Planned concurrent participation in other anti-tumor treatments during the study.
- •Pregnant or breastfeeding women.
研究组 & 干预措施
NK042 - cellular therapy
Phase Ia (Dose Escalation): Determines maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) using single- and multiple-dose escalation with a "3+3" design. Phase Ib (Cohort Expansion): Evaluates safety, tolerability, and efficacy in solid tumor indications that demonstrated preliminary efficacy in Phase Ia. Participants undergo lymphodepletion prior to the first infusion of NK042.
干预措施: NK042
NK042 - cellular therapy
Phase Ia (Dose Escalation): Determines maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) using single- and multiple-dose escalation with a "3+3" design. Phase Ib (Cohort Expansion): Evaluates safety, tolerability, and efficacy in solid tumor indications that demonstrated preliminary efficacy in Phase Ia. Participants undergo lymphodepletion prior to the first infusion of NK042.
干预措施: Cyclophosphamide (CTX)
NK042 - cellular therapy
Phase Ia (Dose Escalation): Determines maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) using single- and multiple-dose escalation with a "3+3" design. Phase Ib (Cohort Expansion): Evaluates safety, tolerability, and efficacy in solid tumor indications that demonstrated preliminary efficacy in Phase Ia. Participants undergo lymphodepletion prior to the first infusion of NK042.
干预措施: Fludarabine (FLU)
结局指标
主要结局
Incidence of Adverse events (AEs) and Serious Adverse Events (SAEs)
时间窗: Up to 1 year after first dose of NK042.
Number of subjects experiencing adverse events, and the frequency and severity of adverse events. The type, frequency, onset, and severity of treatment-emergent adverse events (TEAEs) will be assessed in accordance with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE),version 5.0.
Dose Limiting Toxicities (DLTs)
时间窗: Up to 28-day after first dose of NK042.
Identification of DLTs to determine the maximum tolerated dose (MTD).
Objective Response Rate (ORR)
时间窗: Up to 1 year after first dose of NK042.
The proportion of participants achieving a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).
次要结局
- Peak plasma concentration (Cmax)(Predose, 4, 24, 48, 72, Day 8, Day 15, Day 22, Day 29 post-dose and every 2 months during the treatment follow-up period.)
- Time to reach maximum concentration (Tmax)(Predose, 4, 24, 48, 72 hours, Day 8, Day 15, Day 22, Day 29 post-dose, and every 2 months during the treatment follow-up period.)
- Area under the plasma concentration versus time curve (AUC₀-ₜ)(Predose, 4, 24, 48, 72 hours, Day 8, Day 15, Day 22, Day 29 post-dose, and every 2 months during the treatment follow-up period.)
- Half-life (T₁/₂) of NK042(Predose, 4, 24, 48, 72 hours, Day 8, Day 15, Day 22, Day 29 post-dose, and every 2 months during the treatment follow-up period.)
- Progression-Free Survival (PFS)(Up to 1 year after first dose of NK042 .)
- Overall Survival (OS)(Up to 1 year after first dose of NK042 .)
- Duration of Response (DOR)(Up to 1 year after first dose of NK042 .)
- Disease Control Rate (DCR)(Up to 1 year after first dose of NK042 .)