Trial Title:
Universal Dual-target NKG2D-NKp44 CAR-T Cells in Advanced Solid Tumors
NCT ID:
NCT05976906
Condition:
Advanced Solid Tumors
Conditions: Official terms:
Neoplasms
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Universal Chimeric Natural Killer Receptor Modified T-cells (CNK-UT)
Description:
1. Dose Escalation: After enrollment, participants will recieve preconditioning by
lymphodepletion or not, and then will be treated with CNK-UT cells with a "3 +3"
design to determine the maximum tolerated dose. 3 dose level of CNK-UK cells will be
tested: 4.6E6/kg，1.5E7/kg，4.6E7/kg. The participants will first receive a single
ascending dose(SAD) mode of administration. During the DLT observation period (21
days), if the participants do not experience DLT, they will receive a multiple
ascending dose(MAD) mode of administration.
2. Indications Expansion: It will be carried out after all participants have completed
the DLT observation in the Dose Escalation phase. The target population, dosage and
frequency of drug administration in the indication expansion stage can be adjusted
and determined according to the previous research results.
Arm group label:
CNK-UT cells therapy
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Aged 18 to 70 years (including 18 and 70 years old), male or female;
2. 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).
3. 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);
4. ECOG physical status score 0 or 1;
5. Estimated life expectancy > 12 weeks;
6. 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.
7. 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);
8. Sufficient venous access for intravenous infusion or venous blood collection;
9. 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.
10. participants voluntarily participate in clinical trial; Understand and know this
study, sign an informed consent form, and be willing to follow all experimental
procedures.
Exclusion Criteria:
1. 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.
2. Participants with a history of organ transplantation;
3. 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.
4. 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.
5. 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.
6. 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).
7. Severe bleeding tendency or coagulation dysfunction, or undergoing thrombolytic
therapy.
8. Uncontrollable hypertension, systolic blood pressure >160 mmHg or diastolic blood
pressure >100 mmHg after optimal medical treatment, history of hypertensive crisis
or hypertensive encephalopathy.
9. 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).
10. 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.
11. Active pulmonary tuberculosis (TB), who is receiving anti-tuberculosis treatment or
has received anti-tuberculosis treatment within 1 year before enrollment; human
immunodeficiency virus (HIV) infection, known syphilis infection.
12. Severe infections that are active or poorly controlled clinically. Severe infection
within 4 weeks prior to the initiation of the study, including but not limited to
hospitalization due to infection, bacteremia, or complications of severe pneumonia.
13. Active autoimmune diseases that require systemic treatment (such as the use of
disease relieving drugs, corticosteroids, or immunosuppressants) have occurred
within 2 years prior to the initiation of the study. Allowing the use of alternative
therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal
or pituitary insufficiency), with a known history of primary immunodeficiency.
Patients with only positive autoimmune antibodies need to confirm the presence of
autoimmune diseases based on the judgment of the investigator.
14. Participants who have received local treatment for advanced tumors within 4 weeks
prior to the initiation of the study.
15. Participants who have received radiation therapy within 4 weeks prior to the
initiation of the study. For participants who receive radiation therapy 4 weeks
before the first administration, all of the following conditions must be met before
enrollment: no toxic responses related to radiation therapy, no need to take
glucocorticoids, excluding radiation pneumonia, radiation hepatitis, and radiation
enteritis; palliative radiotherapy for bone metastases lesion is allowed, which must
be completed 2 weeks before enrollment.
16. Participants who have received traditional Chinese medicine with anti-tumor effects
or drugs with immunomodulatory effects (including thymosin, interferon, interleukin,
except for drugs that need to be used locally to control pleural or ascites) within
2 prior to the initiation of the study.
17. Participants who have received adjuvant surgical therapy, chemotherapy (6 weeks for
mitomycin and nitrosourea), targeted therapy, and immunosuppressive therapy 4 weeks
prior to the initiation of the study, such as corticosteroid users;
18. Participants who have received treatment from other clinical trials within 12 weeks
prior to the initiation of the study.
19. Participants who receive attenuated live vaccines within 6 months prior to the
initiation of the study or plan to receive them during the study period.
20. Participants who have undergone major surgery (craniotomy, thoracotomy, or
laparotomy) within 4 weeks prior to the initiation of the study, or have severe
unhealed wounds, ulcers, or fractures.
21. Uncontrolled/uncorrectable metabolic disorders or other non-malignant organ diseases
or systemic diseases or secondary reactions to cancer, which can lead to higher
medical risk and/or uncertainty in survival assessments.
22. Allergic to components of CNK-UT injection.
23. Participants suffer from known mental or substance abuse disorders, which may
interfere with their ability to comply with research requirements.
24. Women who are pregnant or breastfeeding, as well as male or female participants who
have planned for birth within 1 year after receiving medication.
25. Other situations that the participant is identified by the investigator as
unsuitable to participate in the study.
Gender:
Female
Minimum age:
18 Years
Maximum age:
70 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
First affiliated hospital, School of Medicine, Zhejiang University
Address:
City:
Hangzhou
Country:
China
Status:
Recruiting
Contact:
Last name:
Weijia Fang, Doctor
Start date:
May 23, 2023
Completion date:
September 2025
Lead sponsor:
Agency:
Zhejiang University
Agency class:
Other
Source:
Zhejiang University
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05976906
