Gastric CancerEarly Phase 1NCT05583201
NKG2D/CLDN18.2 CAR-T(KD-496) in the Treatment of Advanced NKG2DL+/CLDN18.2+ Solid Tumors
A Early Phase 1 study testing KD-496 in people with Gastric Cancer and Pancreatic Cancer, run by jianming xu at 1 site in China.
Trial summary
This is a Phase 1, single-arm, single-center, open-label study to evaluate the safety and effectiveness of NKG2D/CLDN18.2-based CAR-T cells infusion in the treatment of advanced NKG2DL+/CLDN18.2+ solid tumors. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Gastric Cancer, Pancreatic Cancer, Solid Tumor
- What is being tested?
- KD-496
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteChina
- Study dates
- 13 Oct 2022to 1 Jun 2026
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Patients diagnosed as advanced solid tumors histopathologically or cytologically, such as gastric cancer and pancreatic cancer. 2. Patients fail standard treatment , or cannot tolerate standard treatment, or there is no standard treatment, the standard treatment recommendations refer to the latest version of the guidelines of the national comprehensive cancer network (NCCN) or the guidelines of the Chinese society of Clinical Oncology (CSCO); 3. Age 18-75 years; 4. ECOG score 0-1; 5. Expected survival ≥ 3 months; 6. Patients must meet coagulation parameters and have adequate peripheral venous access for apheresis, and must also have enough PBMC to manufacture CAR T cells; 7. NKG2DL/CLDN18.2 (according to the positive comprehensive score of 0-12 points, positive SCORE of NKG2DL and CLDN18.2 ≥5) positive confirmed by Immunohistochemistry. Biopsy tissue must be no more than 2 year, if not, must obtain new tissue material from a recent surgical or diagnostic biopsy; 8. Eligible organ and bone marrow functions defined as follows:
- Absolute neutrophil count ≥1.5×10^9/L, lymphocyte count ≥0.5×10^9/ L, platelet count ≥90×10^9/L, hemoglobin ≥90g/L (no blood transfusion or Erythropoietin within 7 days);
- Total bilirubin ≤1.5ULN; (Patients with Gilbert syndrome were diagnosed with total bilirubin ≤3mg/dL) Serum alanineamino transferase (ALT) or aspartate aminotransferase(AST)≤3ULN(ALT and AST in patients with liver metastases ≤5ULN);
- Creatinine ≤1.5ULN or eGFR≥60mL /min（Cockcroft and Gault）
- International normalized ratio (INR) ≤1.2;
- Lung function: ≤ grade 1 dyspnea(according to NCI-CTCAE V5.0), SaO2≥91%;
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- Cardiac function:
- Cardiac ejection fraction (LVEF) detected by echocardiography or MUGA ≥50% 1 month before enrollment. 9. Patients must have measurable lesions as defined by RECIST 1.1; 10. If the patient is HBsAg positive or HBcAb positive, HBV-DNA should be < 2000IU/ml. HBsAg positive patients.Antiviral therapy must be received according to the Chronic Hepatitis B Prevention and Treatment Guidelines 2019.
- 11.Patients fully understand the test and voluntarily sign the informed consent; 12. Patient agree to use approved contraceptive methods (e.g., birth control pills, barrier devices, iuds, contraindicated drugs) during the study and for at least 13 months after last cell infusion, until no CAR-T cells were detected by two consecutive PCR tests.
Who cannot join
- Human immunodeficiency virus (HIV), Active hepatitis B (HBV DNA≥500IU/ml) or hepatitis c (anti-HCV positive and HCV RNA higher than the detection limit of analysis method)；
- Patients had received any gene therapy (including CAR-T cell therapy) or any T cell therapy；
- Patients had participated in other drug trials within 4 weeks prior to the study；
- Patients with history or CT examination revealed active tuberculosis infection within 1 year before enrollment or patients diagnosed with active pulmonary tuberculosis 1 year ago without regular treatment；
- Patients with sudden pulmonary disease, interstitial lung disease, pulmonary fibrosis, acute pulmonary disease, etc;
- Subjects with pre-existing or active autoimmune diseases, or those with potential for recurrence (e.g., Wolf erythematosus systemic) Sores, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, multiple sclerosis, vasculitis, kidneyGlomerulonephritis, etc.), or patients at high risk (such as those who have received organ transplants and require immunosuppressive therapy). But allowSubjects with the following diseases were enrolled:
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- 1)Type 1 diabetic patients with stable disease after a fixed dose of insulin; 2)Only autoimmune hypothyroidism on hormone replacement therapy 3)Skin conditions that do not require systemic treatment (e.g., eczema, a rash of up to 10% of the body surface, silver flakes without ophthalmic symptoms Disease,etc.); 4)The use of immunosuppressants, such as steroids, should be phased out before the study begins if the patient has adrenal glands.If they are not functional, corticosteroids can be continued to replace the physiological dose (dose equivalent to ≤10 mg prednisone/day) 7.A history of severe heart disease, including medically poorly controlled hypertension (systolic blood pressure >160mmHg and/or diastolic blood pressure) Pressure >90mmHg), and any of the following conditions occurring within the past 6 months: patients with QT prolongation syndrome, screening,Phase 12 lead ECG results QTc interval >470mSEC, congestive heart failure (New York Heart Association grade ≥Class Ⅲ), cardiac angioplasty and stenting, myocardial infarction, unstable angina pectoris, severe arrhythmia or the researcher assessed heart disease that was not eligible for enrollment.
- 8. Clinically symptomatic brain metastases with the exception of patients with stable, asymptomatic brain metastases treated with radiotherapy or surgery for 14 days.
- 9. Other central nervous system disorders judged by the investigators to be likely to affect the trial: such as epilepsy/seizures, cerebral ischemia/hemorrhage, Dementia, cerebellar disease or autoimmune disease affecting the central nervous system.
- 10.Complicating hematologic malignancy or other primary malignant solid tumors, except in the following cases: 1) Patients with cervical or breast cancer accepted radical therapy without evidence of disease for more than 3 years; 2) The orthotopic tumor was successfully removed without definite resection patients with ≥5 years of evidence of disease.
- 11.Prior to apheresis, he received the following antitumor treatments:
- Cytotoxic treatment within 14 days;
- have received small molecule targeted therapy within 14 days or at least 5 half-lives, whichever is shorter,Therapy or investigational drug therapy, or treatment with invasive investigational medical devices;
- Treatment with monoclonal antibodies within 21 days;
- Immunomodulator therapy within 7 days;
- Radiotherapy within 14 days. 12. Female subjects who are pregnant or breastfeeding during the screening period; 13. With a history of severe hypersensitivity to the primary therapeutic agents used in this study included fludarabine, cyclophosphamide, and PROPHYlaxis during pretreatment Tocilizumab and anti-infective drugs for CRS) 14.Untreated brain metastases or symptoms of brain metastases. 15.Patients with heart disease or poorly controlled high blood pressure who need treatment.
- 16.Patients with unstable or active peptic ulcers or gastrointestinal bleeding. 17.Patients who have a history of organ transplantation or are preparing for organ transplantation.
- 18.Patients requiring anticoagulant therapy (e.g., warfarin or heparin). 19.Patients requiring long-term antiplatelet therapy (aspirin,dose>300mg/d;clopidogrel,dose>75mg/d) 20.Patients had undergone major surgery or serious injury 4 weeks before the start of the study, or would undergo major surgery during the study.
- 21.Toxicity > grade 1 from previous antineoplastic therapy before screening (except alopecia).
- 22.Conditions that other researchers deemed inappropriate for inclusion
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Chinese PLA General Hospital
Beijing
jianming Xu, 13910866712, jianmingxu2014@163.com
About this study
Official title: A Single-center, Open-label, Single-arm Clinical Study of the Safety and Efficacy of KD-496 CAR-T Therapy in Advanced NKG2DL+/CLDN18.2+ Solid Tumors
This is a Phase 1, single-arm, single-center, open-label study to evaluate the safety and effectiveness of NKG2D/CLDN18.2-based CAR-T cells infusion in the treatment of advanced NKG2DL+/CLDN18.2+ solid tumors.
Read the detailed description
This is an open-label, dose escalation/expansion study to assess the safety,tolerability, and efficacy of KD-496 cell infusion in patients with advanced NKG2DL+/CLDN18.2+ solid tumors. In this study, the enrollment of the patients must meet the inclusion and exclusion criteria. All subjects will be undergo screening, pre-treatment (cell product preparation, lymphodepleting chemotherapy), treatment and follow up.
- Conditions
- Gastric Cancer, Pancreatic Cancer, Solid Tumor
- Being tested
- KD-496
- Keywords
- NKG2D, CLDN18.2
- Medical subject headings
- Stomach Neoplasms, Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KD-496Biological
Autologous genetically modified anti-NKG2DL/CLDN18.2 CAR transduced T cells
| Study group | Role | What they receive |
|---|---|---|
| KD-496 cell infusion | Experimental | Each subject will receive KD-496 cell infusion Receives: Biological: KD-496 |
What is being measured
The primary outcome is the main question the study is designed to answer.
treatment-emergent adverse events(TEAEs)
An adverse event is any undesirable experience associated with the use of a medical product in a patient
Measured: 3 months after single infusion
Dose-limiting toxicity (DLT) rate
A drug-related toxicity during treatment with the drug, the severity of which is clinically unacceptable, limiting the further escalation of drug dose.
Measured: 3 months after single infusion
CAR positive T cells in patients
The time of CAR-T cell reach the peak and turn back to baseline
Measured: 6 months after single infusion
Secondary outcomes (3)
Objective response rate(ORR)
objective tumor response rate will be calculated for patients with measurable disease per RECIST 1.1
Measured: 1 month, 2 month, 3 month, 6 month, 1 year after cell infusion
Progression free survival(PFS)
the time from the date of first infusion of the KD-496 to the first documented disease progression (according to RECIST 1.1) or death (due to any cause), whichever occurs first
Measured: 1 month, 2 month, 3 month, 6 month, 1 year after cell infusion
Complete remission (CR)
the time from the date of first infusion of KD-496 to death of the subject
Measured: 1 month, 2 month, 3 month, 6 month, 1 year after cell infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Oct 2022
- Study start13 Oct 2022
- Primary completion1 Jun 2024 (estimated)
- Study completion1 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Gastric CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- jianming xu
- Sponsor type
- University, hospital or other
- Collaborators
- KAEDI
- Responsible party
- Sponsor-investigator, jianming xu, The Affiliated Hospital of the Chinese Academy of Military Medical Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05583201
- Sponsor's protocol ID
- KD-496-XJM
- Status last verified
- Feb 2023
- First submitted
- 13 Oct 2022
- Last updated
- 8 Feb 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-center, Open-label, Single-arm Clinical Study of the Safety and Efficacy of KD-496 CAR-T Therapy in Advanced NKG2DL+/CLDN18.2+ Solid Tumors
- ClinicalTrials.gov ID
- NCT05583201
- Acronym / sponsor ID
- KD-496-XJM
- Conditions
- Gastric Cancer, Pancreatic Cancer, Solid Tumor
- Keywords
- NKG2D, CLDN18.2
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- jianming xuUniversity, hospital or other
- Collaborators
- KAEDI
- Study start
- 13 Oct 2022 (actual)
- Primary completion
- 1 Jun 2024 (estimated)
- Study completion
- 1 Jun 2026 (estimated)
- First posted
- 17 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a Phase 1, single-arm, single-center, open-label study to evaluate the safety and effectiveness of NKG2D/CLDN18.2-based CAR-T cells infusion in the treatment of advanced NKG2DL+/CLDN18.2+ solid tumors.
Detailed description
This is an open-label, dose escalation/expansion study to assess the safety,tolerability, and efficacy of KD-496 cell infusion in patients with advanced NKG2DL+/CLDN18.2+ solid tumors. In this study, the enrollment of the patients must meet the inclusion and exclusion criteria. All subjects will be undergo screening, pre-treatment (cell product preparation, lymphodepleting chemotherapy), treatment and follow up.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| KD-496 cell infusion | Experimental | Biological: KD-496Each subject will receive KD-496 cell infusion |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 1. Patients diagnosed as advanced solid tumors histopathologically or cytologically, such as gastric cancer and pancreatic cancer. 2. Patients fail standard treatment , or cannot tolerate standard treatment, or there is no standard treatment, the standard treatment recommendations refer to the latest version of the guidelines of the national comprehensive cancer network (NCCN) or the guidelines of the Chinese society of Clinical Oncology (CSCO); 3. Age 18-75 years; 4. ECOG score 0-1; 5. Expected survival ≥ 3 months; 6. Patients must meet coagulation parameters and have adequate peripheral venous access for apheresis, and must also have enough PBMC to manufacture CAR T cells; 7. NKG2DL/CLDN18.2 (according to the positive comprehensive score of 0-12 points, positive SCORE of NKG2DL and CLDN18.2 ≥5) positive confirmed by Immunohistochemistry. Biopsy tissue must be no more than 2 year, if not, must obtain new tissue material from a recent surgical or diagnostic biopsy; 8. Eligible organ and bone marrow functions defined as follows:
- Absolute neutrophil count ≥1.5×10^9/L, lymphocyte count ≥0.5×10^9/ L, platelet count ≥90×10^9/L, hemoglobin ≥90g/L (no blood transfusion or Erythropoietin within 7 days);
- Total bilirubin ≤1.5ULN; (Patients with Gilbert syndrome were diagnosed with total bilirubin ≤3mg/dL) Serum alanineamino transferase (ALT) or aspartate aminotransferase(AST)≤3ULN(ALT and AST in patients with liver metastases ≤5ULN);
- Creatinine ≤1.5ULN or eGFR≥60mL /min（Cockcroft and Gault）
- International normalized ratio (INR) ≤1.2;
Key exclusion criteria (20 listed)
- Human immunodeficiency virus (HIV), Active hepatitis B (HBV DNA≥500IU/ml) or hepatitis c (anti-HCV positive and HCV RNA higher than the detection limit of analysis method)；
- Patients had received any gene therapy (including CAR-T cell therapy) or any T cell therapy；
- Patients had participated in other drug trials within 4 weeks prior to the study；
- Patients with history or CT examination revealed active tuberculosis infection within 1 year before enrollment or patients diagnosed with active pulmonary tuberculosis 1 year ago without regular treatment；
- Patients with sudden pulmonary disease, interstitial lung disease, pulmonary fibrosis, acute pulmonary disease, etc;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KD-496Autologous genetically modified anti-NKG2DL/CLDN18.2 CAR transduced T cells | Biological | KD-496 cell infusion |
Primary outcome
treatment-emergent adverse events(TEAEs)
Time frame: 3 months after single infusion
An adverse event is any undesirable experience associated with the use of a medical product in a patient
Dose-limiting toxicity (DLT) rate
Time frame: 3 months after single infusion
A drug-related toxicity during treatment with the drug, the severity of which is clinically unacceptable, limiting the further escalation of drug dose.
CAR positive T cells in patients
Time frame: 6 months after single infusion
The time of CAR-T cell reach the peak and turn back to baseline
3 secondary outcomes
Objective response rate(ORR)
Time frame: 1 month, 2 month, 3 month, 6 month, 1 year after cell infusion
Progression free survival(PFS)
Time frame: 1 month, 2 month, 3 month, 6 month, 1 year after cell infusion
Complete remission (CR)
Time frame: 1 month, 2 month, 3 month, 6 month, 1 year after cell infusion
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing KD-496 in people with Gastric Cancer and Pancreatic Cancer, run by jianming xu at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
treatment-emergent adverse events(TEAEs) (time frame: 3 months after single infusion). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2023.