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| Name | Class |
|---|---|
| Yingkai Saiwei(Beijing)Biotechnology Co., Ltd | UNKNOWN |
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This study is a single center, open, single arm, dose increasing early clinical study. The purpose of this study is to evaluate the safety and efficacy of YK0901 immunotherapy in the treatment of patients with advanced solid tumor whose tumor antigen KRAS G12V expression is positive (HLA-A * 11:01).
KRAS mutations exist in various cancers, especially pancreatic, lung and colorectal cancer. G12V is one of the most common mutation types for KRAS. It's challenging to chemically acquire the targeted drug for this mutation. Recent studies reported that this mutation peptides can form a neoepitope for T cell recognition.Our study aims to evaluate the safety and tolerability of YK0901 TCR-T cell for KRAS G12V positive advanced solid tumors.In this trial, 11 subjects with KRAS G12V mutations and matching HLA-A*11:01 subtypes are recruited for autologous TCR-T therapy.Within 1-7days after pretreatment, subjects will receive a single TCR-T infusion with an infusion dose of about 1×108~5×1010.Once every 12 hours within 24 hours after TCR-T cell infusion, recombinant human interleukin-2 will be injected intravenously for 14 days .
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| YK0901 cells | Experimental | 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| YK0901 cells | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Dose-limiting toxicity (DLT) | 2 years | |
| Treatment related AEs | 2 years |
| Measure | Description | Time Frame |
|---|---|---|
| Antitumor efficacy-Objective response rate (ORR) | 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) |
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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:
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:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| lin shen | Contact | (86)10-88196561 | linshenpku@163.com |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of GI Oncology, Peking University Cancer Hospital | Beijing | China |
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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) | The period from the first infusion to any cause of death | 2 years |
| Antitumor efficacy-Duration of response (DOR) | The period from the first evaluation of CR or PR to the first evaluation of PD or death of any cause | 2 years |