Advanced Solid Tumors
Conditions
Keywords
KRAS G12V, Immunotherapy, T cell, Adoptive cell therapy, T cell receptor, TCR
Brief summary
This is a single-center, open-label, single-arm, dose-escalation study aimed at evaluating the safety and preliminary efficacy of KRAS-specific autologous TCR-T cells in patients with advanced solid tumors harboring KRAS G12V mutation.
Detailed description
CRTKVA11-03 injection was developed based on affinity-optimized KRAS G12V-specific TCR molecules. Its safety and tolerability was explored in a single-center, open-label, single-arm, dose-escalation study. 9 - 18 patients with advanced solid tumors who have KRAS G12V mutation and HLA-A\*11:01 genotype, and have failed standard treatments will be treated wtith CRTKVA11-03 TCR-T injection. The primary objective is to evaluate the safety and tolerability of CRTKVA11-03 in the treatment of advanced malignant solid tumors, the secondary objective is to describe the pharmacokinetic (PK) characteristics of CRTKVA11-03 after infusion into humans, observe their proliferation and persistence in vivo. The key study procedures include leucocyte apheresis and preparation of TCR-T cells, lymphocyte depletion (lymphodepletion), and the infusion of CRTKVA11-03 injection and follow-up.
Interventions
DRUGCRTKVA11-03 TCR-T Cell Injection
Drug1 : Fludarabine + Cyclophosphamide Drug2 :Interleukin 2 Drug3 :CRTKVA11-03 TCR-T Cell Injection
Sponsors
Corregene Biotechnology Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Patients aged 18-70 years. * Histologically or cytologically confirmed advanced solid tumors (e.g., colorectal cancer, pancreatic cancer, NSCLC) with KRAS G12V mutations and HLA-A\*11:01 genotype. * Failed standard therapies or no effective treatment available. * ECOG performance status of 0-1. * Life expectancy of ≥3 months. * Presence of at least one measurable lesion as defined by RECIST 1.1 criteria. * Female patients of childbearing potential must agree to use highly effective contraceptive methods during the study and for at least 6 months after the last dose. A negative pregnancy test within 7 days prior to treatment initiation is required. * Written informed consent provided by the patient, with an expectation of compliance with study procedures.
Exclusion criteria
* Prior treatment with gene-modified T-cell therapies. * Current treatment with T-cell suppressive agents (e.g., cyclophosphamide, FK506, tripterygium glycosides) or T-cell stimulants. * Chemotherapy, targeted therapy, immunotherapy, or investigational drugs administered within 2 weeks, or radiotherapy within 4 weeks prior to enrollment. * Significant organ dysfunction, as evidenced by: * leukocytes\<3.0 x 109/L * absolute neutrophil count \>1.5 x 109/L * hemoglobin\<90g/L * platelets \<100 x 109/L * Creatinine\>1.5×ULN or creatinine clearance \<50mL/min * lymphocytes\<0.5 x 109/L * total bilirubin\>3×ULN; ALT/AST\>3×ULN (or \>5× ULN in patients with liver metastases) * INR/APTT\>1.5×ULN * SpO2≤93% * Presence of serious diseases and comorbidities, including but not limited to: severe heart disease, cerebrovascular disease, seizures, poorly controlled diabetes (such as Type 1 diabetes or insulin-dependent diabetes), pancreatic dysfunction, severe infections, active gastrointestinal ulcers, gastrointestinal bleeding, mechanical or paralytic bowel obstruction, pulmonary fibrosis, renal failure, respiratory failure, etc. * History of severe cardiovascular diseases within the past 6 months, including but not limited to: myocardial infarction, severe or unstable angina, coronary artery or peripheral artery bypass surgery, New York Heart Association (NYHA) Class III or IV heart failure, etc. * Left ventricular ejection fraction (LVEF) \< 50%. * Symptomatic brain metastases unless stabilized with prior treatment (e.g., surgery or radiotherapy). * Known history of myelodysplastic syndrome, lymphoma, or other malignancies. * Known allergy to albumin, investigational drugs, or their excipients. * Active autoimmune diseases, including but not limited to acquired/congenital immunodeficiency, organ transplantation, autoimmune hepatitis, systemic lupus erythematosus, or inflammatory bowel disease. * Active hepatitis B, hepatitis C, or HIV infection. * Pregnancy or breastfeeding. * Uncontrolled mental or neurological disorders. * Any condition deemed unsuitable for study participation by the investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| DLT (Dose Limiting Toxicity) Incidence Rate | 28 days |
| Explore the MTD (Maximum Tolerated Dose) or Subsequent Expansion Dose | 28 days |
| Safety Assessment: Changes in patient safety parameters at various follow-up time points after TCR-T infusion, as well as the incidence of adverse events (AEs), which were graded according to the CTCAE V6.0 severity scale. | 2 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Assessed by RECIST 1.1 | 2 years | — |
| Disease Control Rate (DCR) Assessed by RECIST 1.1 | 2 years | — |
| Duration of Response (DOR) Assessed by RECIST 1.1 | 2 years | — |
| Progression-Free Survival (PFS) Assessed by RECIST 1.1 | 2 years | — |
| Overall Survival (OS) | 2 years | Overall survival was defined as the time from KRAS-Specific Autologous TCR-T Cell infusion to the date of death |
| qPCR Monitoring of TCR-T Cell Copy Numbers in Peripheral Blood | 2 years | — |
Countries
China
Outcome results
None listed