solid Tumors with TP53 or KRAS gene mutations
Conditions
Interventions
vaccine group:synthetic shared-neoantigen biological vaccine and anti-PD(L)1 antibody
Sponsors
Nanjing Drum Tower Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: a. Age =18 and =70 years, ECOG performance status 0-1, expected survival =3 months. b. Histologically confirmed locally advanced unresectable or metastatic solid tumors, genetic testing confirming at least one TP53 or KRAS gene mutation, and at least one measurable lesion for efficacy assessment. Divided into the following four cohorts: Cohort 1: Microsatellite stable colorectal cancer (MSS-CRC) patients currently who currently plan to receive or are currently receiving standard first-line or second-line treatment for no more than three cycles, and who have not experience disease progressed in their initial imaging efficacy evaluation. Cohort 2: Metastatic non-small cell lung cancer (NSCLC) who currently plan to receive or are currently receiving standard with first-line or second-line chemotherapy in combination with an anti-PD-(L)1 antibody for no more than three cycles, and who have not progressed in their initial imaging efficacy evaluation. Cohort 3: Metastatic pancreatic ductal adenocarcinoma (PDA) who plan to receive or are currently receiving first-line chemotherapy for no more than three cycles, and who have not progressed in their initial imaging efficacy evaluation. Cohort 4: Other solid tumors with TP53/KRAS mutations that have progressed after standard treatment, or those who refuse/are intolerant to standard treatment or lack effective standard treatment. c. At least one lesion available for efficacy assessment. d. Patients must meet the following hematologic criteria: d1. Lymphocyte count =0.8×10^9/L, neutrophil count =1.5×10^9/L d2. Hemoglobin =90g/L d3. Platelet count =90×10^9/L e. Patients must meet the following biochemical criteria: e1. Total bilirubin =1.5×upper limit of normal (ULN) e2. AST and ALT <1.5×ULN, or <5×ULN in the presence of liver metastasis e3. Creatinine clearance =60ml/min f. Patients must meet the following coagulation criteria: INR or PTT =1.5×ULN g. Reproductive-age patients must take appropriate contraceptive measures (contraception or other birth control methods) before enrollment and during the trial. h. Signed informed consent. i. Ability to comply with the study protocol and follow-up procedures.
Exclusion criteria
Exclusion criteria: a. Non-small cell lung cancer patients with EGFR, ALK, ROS1, RET, or TRK gene mutations. b. Patients with microsatellite-high (MSI-H) or mismatch repair deficiency (dMMR) solid tumors. c. Patients with active bacterial or fungal infection (Grade =2 NCI-CTC, version 3) or active pulmonary tuberculosis. d. Patients with HIV, HCV, HBV infection, uncontrollable coronary artery disease, asthma, uncontrollable cerebrovascular disease, or other conditions considered by the investigator as ineligible for enrollment. e. Patients with any active autoimmune disease or immune deficiency; patients with vitiligo. f. Patients currently using immunosuppressive agents or systemic corticosteroid therapy for immunosuppressive purposes (dose >10mg/day of prednisone or equivalent), and still continuing use within 2 weeks before enrollment. g. Poorly controlled clinical symptoms or diseases of the heart, such as: NYHA class 2 or above heart failure; Unstable angina; Myocardial infarction within the past year; Clinically significant supraventricular or ventricular arrhythmias requiring treatment or intervention; QTc >450ms (males); QTc >470ms (females). h. Abnormal coagulation function (INR >2.0, PT >16s), bleeding tendency, or receiving thrombolytic or anticoagulant therapy, with allowance for prophylactic use of low-dose aspirin or low molecular weight heparin. i. Patients with active infection, unexplained fever =38.5°C within 7 days before medication, or baseline white blood cell count >15×10^9/L; or purulent and chronic infections with non-healing wounds. j. Uncontrollable pleural effusion, pericardial effusion, and abdominal effusion (requiring drainage at least once a month). k. The patient has a history of other tumors, except for in situ cervical cancer, treated squamous cell carcinoma or bladder epithelial tumors (Ta and TIS), or other malignant tumors that have undergone curative treatment (at least 5 years prior to enrollment). l. A history of gastrointestinal perforation and/or fistula within 6 months, a history of intestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colon resection or extensive small intestine resection with concurrent chronic diarrhea), Crohn's disease, ulcerative colitis, or long-term chronic diarrhea. m. Subjects who experience gastrointestinal bleeding or have a high risk of bleeding within 2 weeks prior to enrollment. n. Subjects with central nervous system metastasis who have symptoms and require clinical intervention. o. Pregnant or lactating women. Reproductive-age women must test negative for pregnancy within 7 days before enrollment. p. Substance abuse, clinical or psychological factors affecting informed consent or study implementation. q. Individuals with a possible allergy to drugs used in immunotherapy. r. Participants unable to undergo immunological and clinical follow-up assessments. s. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation. t. Participants concurrently participating in other interventional drug clinical trials.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Immunogenicity Testing of the synthetic shared-neoantigen biological vaccine;ORR;DCR;AE;The relationship between immune response and therapeutic effect; | — |
Secondary
| Measure | Time frame |
|---|---|
| mPFS;mOS; | — |
Countries
China
Contacts
Public ContactBaorui Liu
Nanjing Drum Tower Hospital
Outcome results
None listed