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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
76
NK042 is an allogeneic, off-the-shelf cellular therapy derived from healthy donors and enriched with NKR+ NK cells.
Fludarabine (FLU) is administered as a lymphodepletion regimen prior to NK042 infusion.
Cyclophosphamide (CTX) is administered as a lymphodepletion regimen prior to NK042 infusion.
Peking University Cancer Hospital
Beijing, China
RECRUITINGIncidence of Adverse events (AEs) and Serious Adverse Events (SAEs)
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.
Time frame: Up to 1 year after first dose of NK042.
Dose Limiting Toxicities (DLTs)
Identification of DLTs to determine the maximum tolerated dose (MTD).
Time frame: Up to 28-day after first dose of NK042.
Objective Response Rate (ORR)
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).
Time frame: Up to 1 year after first dose of NK042.
Peak plasma concentration (Cmax)
Cmax of NK042 will be measured to determine the maximum concentration reached in the plasma following administration.
Time frame: 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)
Tmax of NK042 will be assessed to determine the time point at which the highest plasma concentration is observed following administration.
Time frame: 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)
AUC₀-ₜ will be assessed to determine the total NK042 exposure from the time of administration (0) to the last measurable concentration (t).
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Time frame: 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
T₁/₂ of NK042 will be assessed to determine the time required for a 50% reduction in the maximum amount of circulating NK042 in the plasma.
Time frame: 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)
The time from the first dose until objective tumor progression or death.
Time frame: Up to 1 year after first dose of NK042 .
Overall Survival (OS)
The time from the first dose until death from any cause.
Time frame: Up to 1 year after first dose of NK042 .
Duration of Response (DOR)
The time from the first documentation of CR or PR to disease progression or death.
Time frame: Up to 1 year after first dose of NK042 .
Disease Control Rate (DCR)
The proportion of participants who achieve a CR, PR, or stable disease (SD) as assessed by RECIST 1.1.
Time frame: Up to 1 year after first dose of NK042 .