- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05933668
Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Solid Tumor
Phase I Clinical Study of YK0901 Injection for the Treatment of Advanced Solid Tumors With HLA-A * 11:01 Positive and KRAS G12V Mutation
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: lin shen
- Phone Number: (86)10-88196561
- Email: linshenpku@163.com
Study Locations
-
-
-
Beijing, China
- Department of GI Oncology, Peking University Cancer Hospital
-
Principal Investigator:
- Lin Shen, PHD
-
Contact:
- lin shen, PhD
- Phone Number: (86)10-88196561
- Email: linshenpku@163.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
1.Age ≥18 years and ≤75 years. 2.Failure on or intolerance to systemic therapy for unresectable advanced cancer.
3.Patients must have at least one measurable lesion defined by RECIST 1.1. 4.Genotype and tumor antigen screening must meet the following two criteria: 1) HLA-A * 11:01 positive; 2) KRAS G12V positive 5.ECOG score 0-1 and expected survival time ≥3 months 6.Patients must meet the following criteria at screening and before preconditioning (baseline). If any laboratory test result is abnormal referring to the following criteria, it is acceptable to test one more time within 1week. If the test result is still abnormal, the patient is screen failed:
- Hematology (no intensive blood transfusion (≥2 times within 1week), platelet transfusion or cell growth factor (except for recombinant erythropoietin) performed within 7days before the test): neutrophils (NE) ≥1.5×109 per liter, lymphocytes (LY) ≥0.5×109per liter (except for before preconditioning), platelets (PLT) ≥75×109per liter and hemoglobin (Hb) ≥8.0 g/dL.
- Blood chemistry: creatinine clearance ≥mL/min, alanine aminotransferase (ALT) ≤2.5×ULN, aspartate aminotransferase (AST) ≤2.5×ULN, total bilirubin (TB) ≤2×ULN, serum lipase and amylase <1.5 ULN, alkaline phosphatase (ALP) ≤2.5 ULN; for patients with bone or hepatic metastasis, AST, ALT and ALP <5ULN.
- Prothrombin time ≤ULN+4 seconds. 7.Women of childbearing potential must have negative serum pregnancy test result at screening and before preconditioning and agree to use an effective and reliable contraceptive method for at least 1 year after the last study treatment. Te acceptable methods include bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusion; any approved oral, injection or implantation of hormone; or barrier contraceptive method: condoms containing spermicidal foam/gel/film/paste /suppositories or occlusive cap (diaphragm or cervical/fornix cap).
8.Voluntarily willing to participate in the study and sign the written informed consent.
9.No systemic anti-tumor therapy received within 2 weeks prior to peripheral blood mononuclear cell (PBMC) collection.
10.Blood oxygen saturation (finger oxygen detection)≥ 95% in a calm and non oxygenated state.
Exclusion Criteria:
- Pregnant or lactating women.
- HIV, treponema pallidum or HCV serology is positive.
- Patients with any uncontrolled active infection, including, but not limited to, active tuberculosis or HBV infection (HBsAg positive or HBV DNA positive).
- Patients with AEs induced by previous treatment that have not recovered to Common Terminology Criteria for Adverse Events (CTCAE) ≤1, except for alopecia and other tolerable events judged by the investigator or permitted laboratory abnormalities according to the protocol.
- Patient allergic or intolerant to preconditioning drugs, including, but not limited to, fudarabine and cyclophosphamide or oxaliplatin; allergic to the components of YK0901; penicillin allergy history confrmed by positive skin test; or any severe allergy history-for example, anaphylactic shock.
- Patients who have a history of organ transplantation or are waiting for organ transplantation.
- Patients who have undergone major surgery or severe trauma within 4weeks before apheresis .
- Patients with other serious diseases that may restrict them from participating in this study, such as poorly controlled diabetes (glycosylated hemoglobin HbA1c >8% undertreatment), poorly controlled hypertension judged by the investigator (blood pressure >160mmHg/100mmHg), severe cardiac insufficiency (left ventricular ejection fraction <50%), myocardial infarction or unstable arrhythmia or unstable angina pectoris, pulmonary embolism, chronic obstructive pulmonary disease, interstitial lung disease or clinically significant lung function test abnormalities in the past 6months.
- Before apheresis and preconditioning, patients who have the following conditions, including, but not limited to: new-onset arrhythmia that cannot be controlled by medications; hypotension that requires the use of vasopressors; or bacterial, fungal or viral infections that require intravenous antibiotic, antiviral or antifungal treatment, and the investigator judged that they are not suitable to continue the experiment. Patients who use antibiotics to prevent infection can continue the study upon the judgment of the investigator
- Patients who are expected to continue using immunosuppressive therapy during the trial (excluding physiological replacement therapy with glucocorticoids, such as prednisone<10mg/d or equivalent doses)
- Patients with central nervous metastases.
- Patients who have participated in other intervention clinical trials within 2 weeks.
- Patients with adverse drug addiction or a history of drug abuse.
- Patient with other malignant tumors within the past 2 years or at the present, except for cervical cancer in situ and basal cell carcinoma of the skin.
- Patients who are unable or unwilling to comply with the clinical protocol, by the investigator's judgment.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: YK0901 cells
Patients will undergo lymphocytapheresis, then treatment with TCR-T cells (at escalating doses) + IL-2.Accelerated titration and "3 + 3" dose escalation were used in this trial .
Five dose levels were set up: the dose level was 1: 1× 108 ± 20%(8×107~1.2×108); the dose level was 2: 1 × 109 (±20%:8×108~1.2×109); the dose level was 3: 5 × 109 (±20%:4×109~6×109); the dose level was 4: 2 × 1010 (±20%:1.6×1010~2.4×1010);
the dose level was 5: 5 × 1010 (±20%:4×1010~6×1010).
|
On day 0, the TCR-T cells will be administered one time.
Drug: Fludarabine + Cyclophosphamide+Oxaliplatin Fludarabine: 25mg/m²/day×3days Cyclophosphamide: 300mg/m²/day×3 days Oxaliplatin:100mg×1day Drug: IL-2 After 18-24 hours of infusion of YK0901 cells, the patients will be given a small dose of IL-2 subcutaneously, 500,000 IU/time, twice a day (interval 10-12 hours), for 14 days.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Dose-limiting toxicity (DLT)
Time Frame: 2 years
|
2 years
|
Treatment related AEs
Time Frame: 2 years
|
2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Antitumor efficacy-Objective response rate (ORR)
Time Frame: 2 years
|
The number of cases in which tumor size is reduced to PR or CR / the total number of evaluable cases (%).
|
2 years
|
Antitumor efficacy-Progression-free survival (PFS)
Time Frame: 2 years
|
The period from the day when the subject receives the infusion of cells to the first recorded tumor progression (whether treated or not) or death of any cause, which occurs first.
|
2 years
|
Antitumor efficacy-Overall survival (OS)
Time Frame: 2 years
|
The period from the first infusion to any cause of death
|
2 years
|
Antitumor efficacy-Duration of response (DOR)
Time Frame: 2 years
|
The period from the first evaluation of CR or PR to the first evaluation of PD or death of any cause
|
2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- YK0901
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Advanced Solid Tumor
-
Aadi Bioscience, Inc.RecruitingAdvanced Solid Tumor | Tumor | Tumor, SolidUnited States
-
BeiGeneRecruitingSolid Tumor | Advanced Solid TumorUnited States, New Zealand, Australia, China
-
Impact Therapeutics, Inc.RecruitingSolid Tumor | Advanced Solid TumorChina, Taiwan, United States, Australia
-
Pyxis Oncology, IncRecruiting
-
Neurogene Inc.Merck Sharp & Dohme LLCActive, not recruitingSolid Tumor | Advanced Solid TumorUnited States, Australia, Canada
-
EMD Serono Research & Development Institute, Inc.Merck KGaA, Darmstadt, GermanyCompletedSolid Tumor | Advanced Solid TumorSpain, United States, Netherlands, United Kingdom
-
Zhuhai Yufan Biotechnologies Co., LtdRecruitingAdvanced Solid Tumor | Advanced Solid MalignanciesChina
-
Zhuhai Yufan Biotechnologies Co., LtdRecruitingAdvanced Solid Tumor | Advanced Solid MalignanciesUnited States
-
GI Innovation, Inc.RecruitingAdvanced Solid Tumor | Metastatic Solid TumorKorea, Republic of, United States
-
Xenthera, Inc.Not yet recruitingAdvanced Solid Tumor | Metastatic Solid Tumor
Clinical Trials on YK0901 cells
-
Medical College of WisconsinMiltenyi Biomedicine GmbHActive, not recruitingB-cell Chronic Lymphocytic Leukemia | B-cell Non Hodgkin LymphomaUnited States
-
University College, LondonUnknownTendinopathy | Achilles Tendinitis | Achilles Degeneration | Achilles Tendinitis, Right Leg | Achilles Tendon Thickening | Achilles Tendinitis, Left LegUnited Kingdom
-
Chongqing Public Health Medical CenterZhejiang Qixin Biotech; Chongqing Sidemu BiotechUnknown
-
Hadassah Medical OrganizationCompletedAmyotrophic Lateral Sclerosis
-
American CryoStem CorporationTerminatedMultiple SclerosisCayman Islands
-
UNC Lineberger Comprehensive Cancer CenterRecruitingNeoplasms | Immune System Diseases | Neoplasms by Histologic Type | Lymphoma | Lymphoproliferative Disorders | Lymphatic Diseases | Immunoproliferative Disorders | Lymphoma, Non-HodgkinUnited States
-
The Second Affiliated Hospital of Fujian Medical...Shanghai iCELL Biotechnology Co., Ltd, Shanghai, ChinaUnknown
-
Guangzhou General Hospital of Guangzhou Military...UnknownParkinson's DiseaseChina
-
University of PennsylvaniaActive, not recruitingRefractory Acute Lymphoblastic Leukemia | Chemotherapy Resistant Acute Lymphoblastic LeukemiaUnited States
-
UNC Lineberger Comprehensive Cancer CenterNational Heart, Lung, and Blood Institute (NHLBI)Active, not recruitingNeoplasms | Immune System Diseases | Neoplasms by Histologic Type | Lymphoma | Lymphoproliferative Disorders | Lymphatic Diseases | Immunoproliferative Disorders | Lymphoma, Non-Hodgkin | Hodgkin DiseaseUnited States