A Study to Evaluate the Safety, Tolerability, Preliminary Efficacy, Pharmacodynamics and Immunogenicity of Universal CNK-UT Cells in Patients With Advanced Solid Tumors.

Zhejiang University1 site in 1 country36 target enrollmentMay 23, 2023

ConditionsAdvanced Solid Tumors

Overview

Phase: Phase 1
Intervention: Not specified
Conditions: Advanced Solid Tumors
Sponsor: Zhejiang University
Enrollment: 36
Locations: 1
Primary Endpoint: Incidence of Treatment Related adverse events (AEs)
Status: Recruiting
Last Updated: 2 years ago

Overview Investigators Eligibility Criteria Outcomes Sites Similar Trials

Overview

Brief Summary

This is a single arm, open-label, multi-center, phase I study to evaluate the safety, tolerability, preliminary efficacy, pharmacodynamics and immunogenicity of universal chimeric natural killer receptor modified T-cells (CNK-UT) targeting NKG2D-Ligands and NCR2-Ligands with or without lymphodepletion in advanced solid tumors.

Detailed Description

This is a single arm, open-label, multi-center, phase I, dose escalation/indications expansion study to assess the safety and tolerability of CNK-UT cells therapy, and to obtain the preliminary efficacy, pharmacodynamics and immunogenicity result in participants who have been diagnosed with advanced solid tumors and failed to standard systemic treatment.

Registry

clinicaltrials.gov

Start Date

May 23, 2023

End Date

September 2025

Last Updated

2 years ago

Study Type

Interventional

Study Design

Single Group

Sex

Female

Investigators

Sponsor

Zhejiang University

Responsible Party

Principal Investigator

Weijia Fang, MD

Director

Zhejiang University

Eligibility Criteria

Inclusion Criteria

•Aged 18 to 70 years (including 18 and 70 years old), male or female;
•Participants with advanced solid tumor diagnosed by histology or cytology (or patients with clinically diagnosed hepatocellular carcinoma) have recurrence or disease progression after first or second-line treatment (with metastasis not excluded). Either the existing standard regimen has failed or cannot be tolerated, or the researchers believe that the participants are not suitable for standard treatment for medical reasons (The Dose Escalation Stage is not limited to the types of tumors, including but not limited to advanced hepatocellular carcinoma, advanced colorectal cancer, advanced cholangiocarcinoma, advanced renal cell carcinoma, advanced triple negative breast cancer, melanoma, sarcoma etc. The Indications Expansion Stages include advanced hepatocellular carcinoma, advanced colorectal cancer, advanced cholangiocarcinoma, advanced renal cell carcinoma, advanced triple negative breast cancer, melanoma, sarcoma).
•According to the RECIST 1.1, there is at least one measurable target lesion, or a measurable lesion with definite progression after local treatment (based on RECIST v1.1 standard);
•ECOG physical status score 0 or 1;
•Estimated life expectancy \> 12 weeks;
•Adequate organ and bone marrow function, and the laboratory test value meets the following requirements within 7 days before enrollment, as follows:
•Blood Routine Test: Absolute neutrophil count (ANC)≥1.0×10\^9/L; Platelet count ≥75×10\^9/L; Haemoglobin≥9.0 g/dL; Hepatic function：Total bilirubin≤3×ULN; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)≤5×ULN; Serum albumin≥28 g/L; Renal function: Serum creatinine≤1.5×ULN, or Creatinine clearance rate (CCR)≥60 mL/min (Cockroft-Gault formula); Coagulation function: International normalized ratio (INR)≤1.5×ULN.
•All toxic responses originating from previous radiotherapy, chemotherapy, or other treatments (occurring within 4 weeks or 5 half-lives of anti-tumor drugs therapy \[including but not limited to chemotherapy, targeted therapy, immunotherapy, Chinese herbal medicine\]) have returned to NCI CTCAEV5.0 Grade≤1 (except for hair loss);
•Sufficient venous access for intravenous infusion or venous blood collection;
•Female participants of childbearing age must undergo a serum or urine pregnancy test before enrollment, and the results must be negative, and agree to take acceptable measures to minimize the possibility of pregnancy during the trial; For female participants of childbearing age or male participants whose sexual partners are women of childbearing age, effective contraceptive measures should be taken during the study and for at least 6 months following the last dose of the study cells infusion.

Exclusion Criteria

•Suffering from other malignant tumors or diagnosed within 5 years before enrollment, excluding radical skin basal cell carcinoma, skin squamous cell carcinoma, thyroid cancer, breast cancer (ductal carcinoma in situ) and / or radical resection of carcinoma in situ.
•Participants with a history of organ transplantation;
•Participants with symptomatic central nervous system (CNS) metastasis confirmed by imaging or pathological examination and clinically unstable for at least 14 days prior to randomization who require steroid treatment.
•Presence of gastroesophageal variceal hemorrhage caused by portal hypertension in the past 3 months; evidence of portal hypertension, assessed by researchers as having a high risk of bleeding.
•Presence of any life-threatening bleeding occurred in the past 3 months, including the need for blood transfusion, surgery or local treatment, and continuous drug treatment.
•Presence of arterial and venous thromboembolism events in the past 6 months, including myocardial infarction, unstable angina, cerebrovascular accident or transient ischemic attack, pulmonary embolism, deep vein thrombosis or any other serious thromboembolism history. Except for implantable intravenous infusion port or catheter-derived thrombosis, or superficial venous thrombosis, thrombus stability after routine anticoagulant therapy.Allow prophylactic use of small doses of low molecular weight heparin (such as enoxaparin 40 mg/day).
•Severe bleeding tendency or coagulation dysfunction, or undergoing thrombolytic therapy.
•Uncontrollable hypertension, systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg after optimal medical treatment, history of hypertensive crisis or hypertensive encephalopathy.
•Symptomatic congestive heart failure (New York Heart Association Class II-IV). Symptomatic or poorly controlled arrhythmia. History of congenital long QT syndrome or corrected QTc \> 500ms during screening (calculated by Fridericia method).
•Participants with pulmonary diseases such as pulmonary fibrosis history, interstitial pneumonia, pneumoconiosis, drug-related pneumonia, severe lung function impairment, and Participants with COVID-19 and severe lung function damage caused by viral infection.