A Phase I Study of NK042 Cell Injection in Advanced Solid Tumors (NKSOLID)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Biological: NK042; Drug: Fludarabine (FLU); Drug: Cyclophosphamide (CTX)

Detailed Description

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
• Enrollment (Estimated): 76
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yongling Fu; Phone Number: +0086 02150888199; Email: yongling.fu@nk-celltech.com

Study Locations

• China
  • Beijing, China, 100142
    • Recruiting
    • Peking University Cancer Hospital
    • Principal Investigator: Lin Shen, MD
    • Contact: Changsong QI, MD; Phone Number: +0086010-88196561; Email: xiwangpku@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntary signing of a written informed consent form.
2. Age between 18 and 70 years.
3. 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.
4. At least one assessable tumor lesion according to Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1).
5. Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1.
6. Expected survival ≥12 weeks.
7. Must have adequate bone marrow, liver, and renal function.

Exclusion Criteria:

1. Insufficient washout period for prior anti-tumor treatments before the first dose, including chemotherapy, targeted therapy, antibody therapy, and radiotherapy.
2. Participation in another clinical trial and use of investigational drugs within 28 days before the first dose.
3. Requirement for anticoagulation therapy.
4. Symptomatic brain parenchymal metastases with less than 4 weeks of stability after treatment.
5. Active pulmonary diseases, including but not limited to interstitial lung disease, pneumonitis.
6. Uncontrolled active infections.
7. Uncontrollable massive pleural effusion, ascites, or pericardial effusion.
8. Previous receipt of other cellular therapies.
9. Planned concurrent participation in other anti-tumor treatments during the study.
10. Pregnant or breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

Biological: NK042; NK042 is an allogeneic, off-the-shelf cellular therapy derived from healthy donors and enriched with NKR+ NK cells.; Drug: Fludarabine (FLU); Fludarabine (FLU) is administered as a lymphodepletion regimen prior to NK042 infusion.; Drug: Cyclophosphamide (CTX); Cyclophosphamide (CTX) is administered as a lymphodepletion regimen prior to NK042 infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence 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.	Up to 1 year after first dose of NK042.
Dose Limiting Toxicities (DLTs)	Identification of DLTs to determine the maximum tolerated dose (MTD).	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).	Up to 1 year after first dose of NK042.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Peak plasma concentration (Cmax)	Cmax of NK042 will be measured to determine the maximum concentration reached in the plasma following administration.	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.	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).	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.	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.	Up to 1 year after first dose of NK042 .
Overall Survival (OS)	The time from the first dose until death from any cause.	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.	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.	Up to 1 year after first dose of NK042 .

Collaborators and Investigators

• Sponsor: Shanghai NK Cell Technology Co., LTD
• Investigators: Principal Investigator: Lin Shen, MD, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Actual): February 7, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: January 6, 2025
• First Submitted That Met QC Criteria: January 12, 2025
• First Posted (Actual): January 14, 2025

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: April 3, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Cell Therapy; Advanced solid tumors; CAR-NK; Early-phase clinical trial
• Additional Relevant MeSH Terms: Neoplasms; Organic Chemicals; Hydrocarbons; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Cyclophosphamide; fludarabine
• Other Study ID Numbers: NK042-I-ST-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No