Advanced malignant solid tumor
Conditions
Interventions
Dose escalation of monotherapy:Preset three dose levels: low, medium and high. Each treatment cycle was set at 3 weeks (Q3W), with administration on the first day of each cycle. After 9 cycles, the ad
Single-drug dose expansion:Select 1 to 2 dose levels that are no higher than the currently proven safe and tolerable for dose expansion studies. Each treatment cycle lasts for 3 weeks (Q3W), with admi
Sponsors
Zhejiang Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 999 Years
Inclusion criteria
Inclusion criteria: 1. The subjects should understand and abide by the relevant research procedures and voluntarily sign the informed consent form; 2. Age >=18 years old, gender not limited; 3. Subjects with locally advanced or metastatic solid tumors confirmed by pathology and carrying KRAS (G12C, G12D, G12V or G13D) mutations; KRAS mutation information can be sourced from: -Previously conducted KRAS gene testing can provide KRAS mutation diagnosis reports from existing medical institutions/diagnostic institutions. -For those who have not undergone KRAS gene testing in the past, tumor tissue specimens and blood samples need to be sent to the central laboratory for testing first. 4. For patients with locally advanced or metastatic solid tumors, if the disease progresses as evaluated by imaging and there is no standard treatment plan or standard treatment has failed or standard treatment cannot be obtained; 5. At least one measurable tumor lesion must be present during screening [in accordance with RECIST V1.1 criteria]. For lesions that have previously received radiotherapy or other local treatments, disease progression must be confirmed by imaging before they can be regarded as measurable lesions. 6. Eastern Cooperative Oncology Group (ECOG) Performance Status Score: 0 or 1 point; 7. Expected survival period >=3 months; 8. The functions of vital organs meet the following criteria (no blood components or cell growth factors have been used within 14 days prior to the start of the study and treatment) : a) Blood routine: Neutrophil count (ANC) >=1.5×10^9/L, lymphocyte count (LYM) >=0.5×10^9/L, platelet count (PLT) >=100×10^9/L, hemoglobin (Hb) >=90g/L; b) Blood biochemistry: Total bilirubin (TBIL) =30g/L Serum creatinine (Scr) 1.5×ULN, the estimated creatinine clearance rate (Clcr) using the Cockcroft-Gault (C-G) formula is greater than 50mL/min. Or the glomerular filtration rate (eGFR) estimated using the Modified Diet for Kidney Disease (MDRD) equation is greater than 50 mL/min; c) Coagulation routine: International Normalized ratio (INR) =50%; 9. Female subjects with fertility must undergo a serum pregnancy test within 7 days before the first dose of the vaccine, and the result must be negative, and they must not be in the lactation period. 10. Female subjects of fertility and male subjects whose partners are women of childbearing age must agree to comply with contraceptive requirements from the date of signing the informed consent form until 6 months after the end of the last treatment.
Exclusion criteria
Exclusion criteria: 1. Received immune cell or tumor vaccine treatment, including but not limited to tumor-infiltrating lymphocytes (TILs), chimeric antigen receptor T/NK cells (CAR-T/NK), T-cell receptor chimeric T cells (TCR-T), and therapeutic tumor vaccines, etc. 2. It is planned to receive live attenuated vaccines during the screening period or the study period and within 90 days after the end of the study drug treatment (inactivated vaccines are allowed). 3. Those who have experienced immune-related adverse reactions after permanent drug withdrawal in the past; 4. Autoimmune diseases in the active stage or requiring long-term immunosuppressant treatment (including but not limited to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide and anti-TNF -a drugs), except for the following situations: -Patients with chronic obstructive pulmonary disease (COPD) or asthma who are receiving mineralocorticoids (such as fludrocortisone), inhaled or low-dose corticosteroids (prednisone =15mg/ day or equivalent doses of similar drugs); -Patients with orthostatic hypotension or adrenal insufficiency treated with low-dose corticosteroids; 5. There is a known history of epilepsy or other symptomatic neurological disorders; 6. Active brain metastases with clinical symptoms at the time of screening or in the past. The following situations are excluded: a. Asymptomatic brain metastasis with the brain metastasis lesion < 1cm and no edema band around it; b. Brain metastases have received treatment with stable symptoms, and imaging examinations show that they have been stable for at least 4 weeks before the first dose of the vaccine and do not require glucocorticoid or anticonvulsant drug treatment; 7. There is a known history of abuse of psychotropic substances, alcohol abuse or drug use; 8. There is evidence of active tuberculosis infection within one year before the screening period and during the screening period, regardless of whether treatment has been received; 9. Patients with a history of (non-infectious) interstitial lung disease (ILD)/non-infectious pneumonia requiring steroid treatment within 6 months prior to the first dose of the vaccine, or those currently suffering from interstitial lung disease requiring treatment or pulmonary fibrosis, pneumoconiosis, radiation pneumonitis, severely impaired lung function, etc., which may interfere with the detection and management of suspected drug-related lung toxicity; 10. Having suffered from other malignant tumors within the past five years, except for the following situations: cutaneous basal cell carcinoma, superficial bladder cancer, cutaneous squamous cell carcinoma, papillary thyroid carcinoma, prostate carcinoma in situ or cervical carcinoma in situ that have been cured for two years before the first administration of the study drug, and no or expected no other treatment was needed during the study period; 11. Those who have a history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation, or have undergone autologous transplantation within 3 months prior to screening; 12. Known to be allergic to the research drug or any of its excipients, or have a history of severe allergic reactions to other vaccines; 13. Suffering from congenital or acquired immune deficiency Such as cellular immune deficiencies (such as DiGeorge syndrome, T-negative severe combined immunodeficiency [SSCID]) or combined T-cell and B-cell immune deficiencies (such as T- and B-negative combi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and Tolerability; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pharmacokinetic;Immunogenicity;Preliminary therapeutic effect; | — |
Countries
China
Contacts
Public ContactZhengbo Song
Zhejiang Cancer Hospital
Outcome results
None listed