Advanced Solid TumorPhase 1NCT05933668
Mutant KRAS G12V-specific TCR Transduced T Cell Therapy for Advanced Solid Tumor
A Phase 1 study testing YK0901 cells in people with Advanced Solid Tumor, run by Peking University at 1 site in China.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced Solid Tumor
- What is being tested?
- YK0901 cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteChina
- Study dates
- Jul 2023to Jul 2026
- Phase
- 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.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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Department of GI Oncology, Peking University Cancer Hospital
Beijing
lin shen, PhD, (86)10-88196561, linshenpku@163.com
lin shen, phD
About this study
Official title: Phase I Clinical Study of YK0901 Injection for the Treatment of Advanced Solid Tumors With HLA-A * 11:01 Positive and KRAS G12V Mutation
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).
Read the detailed description
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 .
- Conditions
- Advanced Solid Tumor
- Being tested
- YK0901 cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
YK0901 cellsBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| 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）. Receives: Biological: YK0901 cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity (DLT)
Measured: 2 years
Treatment related AEs
Measured: 2 years
Secondary outcomes (4)
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 (%).
Measured: 2 years
Antitumor efficacy-Progression-free survival (PFS)
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.
Measured: 2 years
Antitumor efficacy-Overall survival (OS)
The period from the first infusion to any cause of death
Measured: 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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2023
- Study startJul 2023 (estimated)
- Primary completionJul 2024 (estimated)
- Study completionJul 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Solid TumorStudies of the same condition, open and under way.
- More trials run by Peking UniversityThe sponsor's other registered studies.
- 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University
- Sponsor type
- University, hospital or other
- Collaborators
- Yingkai Saiwei（Beijing）Biotechnology Co., Ltd
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05933668
- Sponsor's protocol ID
- YK0901
- Status last verified
- Jun 2023
- First submitted
- 27 Jun 2023
- Last updated
- 6 Jul 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 6 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Clinical Study of YK0901 Injection for the Treatment of Advanced Solid Tumors With HLA-A * 11:01 Positive and KRAS G12V Mutation
- ClinicalTrials.gov ID
- NCT05933668
- Acronym / sponsor ID
- YK0901
- Conditions
- Advanced Solid Tumor
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 11 participants (estimated)
- Lead sponsor
- Peking UniversityUniversity, hospital or other
- Collaborators
- Yingkai Saiwei（Beijing）Biotechnology Co., Ltd
- Study start
- Jul 2023 (estimated)
- Primary completion
- Jul 2024 (estimated)
- Study completion
- Jul 2026 (estimated)
- First posted
- 6 Jul 2023 (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 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).
Detailed description
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 .
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| YK0901 cells | Experimental | Biological: YK0901 cellsPatients 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）. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (15 listed)
- 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.
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 |
|---|---|---|
| YK0901 cellsOn 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. | Biological | YK0901 cells |
Primary outcome
Dose-limiting toxicity (DLT)
Time frame: 2 years
Treatment related AEs
Time frame: 2 years
4 secondary outcomes
Antitumor efficacy-Objective response rate (ORR)
Time frame: 2 years
Antitumor efficacy-Progression-free survival (PFS)
Time frame: 2 years
Antitumor efficacy-Overall survival (OS)
Time frame: 2 years
Antitumor efficacy-Duration of response (DOR)
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 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 Phase 1 study testing YK0901 cells in people with Advanced Solid Tumor, run by Peking University 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 8 inclusion and 15 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 6 Jul 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Contact lin shen ((86)10-88196561, linshenpku@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicity (DLT) (time frame: 2 years). The study lists 2 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 6 Jul 2023.