A Phase I Platform Study of Target-Based Screened CAR-Macrophages for the Treatment of Advanced Malignant Tumors

NCT07409766 | Not Yet Recruiting Early Phase 1 DMC

• 1 other identifier: NCC5975
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label, single-center, dose-escalation platform clinical trial design. Using an adenovirus vector platform, the study aims to evaluate the safety, tolerability, pharmacokinetic characteristics, and preliminary anti-tumor activity of investigational CAR-M macrophage injections targeting various antigens (including HER2, PSMA, FAP, etc.) in patients with advanced solid tumors. The clinical trial is designed to be conducted in cohorts, with patients enrolled into respective cohorts based on target antigen and indication screening

Conditions

Advanced Malignant Tumors

Outcome Measures

Primary Outcomes (3)

• Incidence of Dose-Limiting Toxicities (DLTs)

  Incidence and characteristics of DLTs graded according to NCI CTCAE v5.0. The DLT observation period is 28 days post-infusion.

  Within 28 days after the first infusion

• Incidence of Adverse Events (AEs)

  Incidence and severity of treatment-emergent adverse events (TEAEs) graded according to NCI CTCAE v5.0.

  From signing ICF until 24 months after the last infusion.

• Determine and characterize the optimal dosing regimen (full dose vs. split dose).

  Split dose is superior for CAR-M optimal dosing: it mitigates acute toxicities (e.g., cytokine responses) via gradual immune activation, sustains robust CAR-M cell expansion and in vivo persistence, and improves safety in high-risk patients. Full dose enables rapid therapeutic efficacy in low-risk cohorts with intact organ function. Optimal regimens are tailored to patient baseline status/indications, validated via dose-escalation trials for balance of safety and anti-tumor activity.

  Day 0, Day 7, Day 14

Secondary Outcomes (8)

• To obtain the pharmacokinetic (PK) characteristics of CAR-M (targeting HER2, PSMA, FAP, etc.) injection in humans.

  Day 0, Day 7, Day 14, Day 21, Day 28

• Serum Cytokines of CAR-M (targeting HER2, PSMA, FAP, etc.) injection in humans.

  0 hours, 6 hours, 24 hours, and 72 hours after each infusion.

• Tumor Microenvironment (TME) Infiltration

  24 hours post-infusion, Day 7 (peak activity), Day 28, and Day 90

• Dynamic Monitoring of Target Expression

  Screening Phase, Day 28, Day 90

• ORR (Objective Response Rate)

  Day 28、Month 3、Month 6、Month 9、Month 12

Study Arms (2)

Cohort 1: Split-dose administration

EXPERIMENTAL

Total dose: 5.0×10⁹ cells Day 1: 50% of the total dose Day 7: The remaining 50% of the dose \[only if no ≥Grade 2 chronic kidney syndrome/nephrotoxicity is observed after the first dose\]

Biological: CAR-M

Cohort 2: Bolus administration

EXPERIMENTAL

Total dose: 5.0×10⁹ cells Day 1: Full dose

Biological: CAR-M

Interventions

CAR-M BIOLOGICAL

IV

Cohort 1: Split-dose administration; Cohort 2: Bolus administration

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 75 years (inclusive) at the time of signing the informed consent form, with no gender restriction.
• Histologically or cytologically confirmed advanced solid tumor (partial laboratory test results are acceptable):
• HER2-positive: IHC 3+ or IHC 2+ with ISH+ PSMA+++: Intensity score 2+ with proportion ≥ 30%, or intensity score 3+ with proportion ≥ 10% FAP+++: Intensity score 2+ with proportion ≥ 30%, or intensity score 3+ with proportion ≥ 10%
• Disease status:
• Subjects (HER2-targeted): Patients with advanced solid tumor who are refractory to or intolerant of DS-8201 treatment.
• Subjects (PSMA-targeted): Patients with advanced solid tumor who are refractory to or intolerant of first- or second-line treatment.
• Subjects (FAP-targeted): Patients with advanced solid tumor who are refractory to or intolerant of first- or second-line treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
• Life expectancy of at least 3 months (as assessed by the investigator).
• Adequate organ function, defined as follows:
• Hematologic: Hemoglobin ≥ 90 g/L, absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L, platelet count ≥ 80 × 10⁹/L Hepatic: Total bilirubin ≤ 1.5 × upper limit of normal (ULN); aspartate aminotransferase (AST) / alanine aminotransferase (ALT) ≤ 2.5 × ULN (≤ 5 × ULN in patients with liver metastases) Renal: Serum creatinine ≤ 1 × ULN, or creatinine clearance (CrCl) ≥ 50 mL/min (calculated by the Cockcroft-Gault formula) Cardiac: Left ventricular ejection fraction (LVEF) ≥ 50% (assessed by ECHO or MUGA) Pancreatic: Serum amylase / lipase ≤ 1.5 × ULN
• Electrolytes: Corrected calcium, potassium, and magnesium levels within the normal range.
• Subjects must have at least one measurable lesion as defined by RECIST Version 1.1.
• Adequate venous access for apheresis with no contraindications.
• Tolerability to G-CSF: No history of severe hypersensitivity to filgrastim or its biosimilars.

You may not qualify if:

• Known hypersensitivity to CAR-M or any of its excipients.
• History of severe hypersensitivity to filgrastim (G-CSF) or tocilizumab.
• Known history of substance abuse.
• A history of ≥ Grade 3 immune-related adverse events (irAEs) or ≥ Grade 2 immune-related myocarditis following prior immunotherapy.
• Active infection requiring systemic therapy, except for the following conditions: uncomplicated urinary tract infection (UTI) (afebrile and resolved after 3 days of antibiotic therapy) or bacterial pharyngitis (confirmed by GAS testing and treated with appropriate antibiotics).
• HIV infection, active hepatitis B virus (HBV) infection (HBV DNA \> upper limit of normal \[ULN\]), or active hepatitis C virus (HCV) infection (HCV RNA \> ULN).
• History of malignant neoplasm other than the following within the past 5 years:
• Curable malignant neoplasms (e.g., basal cell carcinoma, carcinoma in situ of the cervix/breast, or cutaneous squamous cell carcinoma).
• Malignant neoplasms with a favorable prognosis (e.g., papillary thyroid carcinoma, carcinoma in situ of the skin or breast), regardless of whether they have been cured or not.
• Receipt of other investigational drugs or therapies within 4 weeks prior to the first administration of CAR-M, or ongoing participation in the safety follow-up period of other investigational drugs or therapies.
• Presence of severe, non-healing wounds, ulcers, or fractures within 4 weeks prior to the first administration of CAR-M.
• History of substance abuse or psychiatric disorders.
• History of severe cardiovascular and cerebrovascular diseases, including but not limited to:
• Acute events: myocardial infarction, stroke, or New York Heart Association (NYHA) Class III-IV heart failure within 6 months.
• Thromboembolism: symptomatic deep vein thrombosis or pulmonary embolism (DVT/PE) within 6 months (unless on stable anticoagulant therapy).

Sponsors & Collaborators

• Cancer Institute and Hospital, Chinese Academy of Medical Sciences: lead

Study Sites (1)

National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences

Beijing, 100000, China

Location

Study Officials

• Ning Li, Dr

  Cancer Institute and Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ning Li

CONTACT

8613581809307; lining@cicams.ac.cn

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: CAR-M

Study Record Dates

• First Submitted: February 2, 2026
• First Posted: February 13, 2026
• Study Start: January 31, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)