Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT06026800
Other study ID # SRRSH2023-755-02
Secondary ID
Status Recruiting
Phase Phase 1
First received
Last updated
Start date September 8, 2023
Est. completion date December 31, 2027

Study information

Verified date September 2023
Source Sir Run Run Shaw Hospital
Contact Xiujun Cai, MD
Phone 0086-0571-86006605
Email caixiujunzju@yahoo.com.cn
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to assess the safety, feasibility, and efficacy of personalized mRNA vaccine iNeo-Vac-R01 in combination with first-line treatment in subjects with advanced digestive system neoplasms.


Description:

This is a single-center, open-label, single-arm clinical study of personalized mRNA vaccine iNeo-Vac-R01 in combination with first-line treatment in subjects with advanced digestive system neoplasms.


Recruitment information / eligibility

Status Recruiting
Enrollment 20
Est. completion date December 31, 2027
Est. primary completion date August 31, 2027
Accepts healthy volunteers No
Gender All
Age group 18 Years to 75 Years
Eligibility Inclusion Criteria: 1. Male or female, >/= 18 years old and </= 75 years old, with the ability to understand and provide signed and witnessed informed consent, and agree and are able to comply with protocol requirements. 2. Subjects must have one of the histologically- or cytologically-confirmed advanced (locally advanced or metastatic) digestive system neoplasms, have measurable disease at study entry defined by RECIST v1.1. Subjects must receive at least 4 cycles of standard first-line treatment according to CSCO clinical guidelines. The toxic effects of previous anti-tumor treatments have returned to </= grade 1 defined by NCI-CTCAE v5.0 or to the level specified by the inclusion/exclusion criteria. 3. Expected survival >/= 6 months. 4. ECOG performance status score of 0 ~ 1. 5. Sufficient tumor tissue samples can be obtained from subjects for genetic analysis, with at least 2 puncture tissues with a tumor purity of = 50% required for puncture samples and at least 0.5cm of tissue required for surgical samples. Alternatively, the original gene sequencing data required for tumor neoantigen analysis can be provided, including full exon sequencing data of tumor tissue, transcriptome sequencing data, and full exon sequencing data of peripheral blood. 6. Echocardiographic evaluation: left ventricular ejection fraction (LVEF) >/= 50%. 7. The organ function level must meet the following requirements: absolute neutrophil count (ANC) >/= 1.5 × 10^9/L, platelet count (PLT) >/= 80 × 10^9/L, hemoglobin (Hb) >/= 90 g/L; serum total bilirubin (TBIL) </= 1.5 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) </= 2.5 × ULN (if there is liver metastasis, TBIL </= 3 × ULN, AST, ALT </= 5 ×ULN are allowed), serum albumin >/= 28g/L, serum creatinine </= 1.5 × BUN, Glomerular filtration rate >/= 50mL/min, prothrombin time (PT) and activated partial thromboplastin time (APTT) and international standardized ratio (INR) </= 1.5 × ULN (without anticoagulant therapy) . 8. For women of childbearing potential: having a negative serum or urine pregnancy test within 7 days prior to study initiation, agreement to remain abstinent or use contraceptive measures during the treatment period. 9. For men: agreement to remain abstinent or use contraceptive measures during the treatment period. Exclusion Criteria: 1. Subjects with cancer requiring anti-tumor treatment within the 5 years prior to enrollment in the study (except stage I prostate cancer, cervical cancer in situ, breast cancer in situ, papillary thyroid cancer and non-melanoma skin cancer that have been treated). 2. Subjects who received major surgery, or had obvious traumatic injury or long-term untreated wounds or fractures within 2 weeks prior to the first dose of iNeo-Vac-R01. 3. Subjects whose sequencing data was found that there are no new antigens available for individualized immunotherapy after analysis. 4. Subjects who prepare to undergo or have previously received bone marrow transplantation, allogeneic organ transplantation, or allogeneic hematopoietic stem cell transplantation. Subjects who receive other anti-tumor treatments within 2 weeks prior to the first dose of iNeo-Vac-R01, including surgical treatment, chemotherapy, radiation therapy, targeted therapy, endocrine therapy, immunotherapy, biological therapy, interventional therapy, or other clinical trial related treatments. 5. Subjects who need to use immunosuppressants, or systemic or absorbable local glucocorticoids therapy to achieve immunosuppressive effects and continue to use them within 7 days before the first administration (excluding those with daily doses of glucocorticoids less than 10mg of prednisone or doses of other therapeutic glucocorticoids equal to 10mg of prednisone). 6. Subjects with symptomatic or untreated central nervous system metastases, except those underwent complete resection and/or radiotherapy and proven to be stable or improved (confirmed to be stable or improved for at least 4 weeks before the first dose of iNeo-Vac-R01 by CT or MRI, with no evidence of brain edema and no need for glucocorticoids or anticonvulsants. 7. Subjects who received other vaccines within 4 weeks before the first dose of iNeo-Vac-R01, and are expected to receive other vaccines during treatment period of the study or within 60 days after the last dose of iNeo-Vac-R01. 8. Subjects who have an active infection or uncontrollable infection requiring systemic treatment, including fungi, bacteria, viruses, or other infections; subjects with active tuberculosis; 9. Subjects with positive hepatitis B surface antigen (HBsAg) and/or positive hepatitis B core antibody (HBcAb) and positive hepatitis B virus DNA titer detection greater than normal range; positive hepatitis C virus (HCV) antibody and HCV RNA detection greater than normal range; positive human immunodeficiency virus antibody; positive treponema pallidum-specific antibody. 10. Subjects with autoimmune diseases or immune deficiencies treated with immunosuppressive drugs, except vitiligo, type 1 diabetes, autoimmune hypothyroidism requiring hormone treatment and psoriasis not requiring systemic treatment; known history of primary immunodeficiency. 11. Subjects with cardiocerebrovascular events: previously or currently heart valve disease >/= grade 3, heart failure within 8 weeks before the first dose of iNeo-Vac-R01 (New York Heart Association [NYHA] cardiac function >/= grade II, myocardial infarction, unstable angina, stroke, transient ischemic attack, cardiac surgery (including coronary artery bypass grafting or percutaneous coronary intervention) within 8 weeks before the first dose of iNeo-Vac-R01, concomitant severe electrocardiogram abnormalities (such as ventricular flutter, ventricular fibrillation, multiform ventricular tachycardia, sick sinus syndrome, third degree atrioventricular block without pacemaker treatment, QTc >/= 480ms, and other conditions evaluated by the investigators as severe abnormalities), hypertension with poor drug control (systolic blood pressure >/= 160mmHg and/or diastolic blood pressure >/= 100mmHg), or other cardiocerebrovascular diseases that have been evaluated by the investigators as unsuitable for participation in this trial. 12. Subjects with respiratory disease: previously or currently pulmonary fibrosis, interstitial lung disease, pneumoconiosis, radiation pneumonia, drug-related pneumonia, severe asthma, pulmonary hypertension or severe impairment of lung function, etc. 13. Subjects with moderate to severe ascites with clinical symptoms; uncontrolled or moderate to equal amounts of pleural effusion and pericardial effusion. 14. Subjects with drug abuse; clinical or psychological or social factors that affect informed consent or research implementation. 15. Subjects with a history of allergies to immunotherapy or vaccines, or other potential immunotherapy allergies identified by the investigators. 16. Subjects identified that it is not suitable for enrollment or may not be able to complete this experiment for other reasons by the investigators. 17. Vulnerable groups, including individuals with mental illness, cognitive impairment, critical patients, minors, pregnant or lactating women, etc.

Study Design


Intervention

Biological:
iNeo-Vac-R01
Personalized mRNA vaccine encoding neoantigen, IH injection

Locations

Country Name City State
China Department of General Surgery, Institute of Minimally Invasive Surgery, Sir Run Run Shaw Hospital Hangzhou Zhejiang

Sponsors (2)

Lead Sponsor Collaborator
Sir Run Run Shaw Hospital Hangzhou Neoantigen Therapeutics Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants with Adverse Events (AEs) [safety and tolerability] 21 days after last iNeo-Vac-R01 dose
Secondary Overall Survival (OS) OS is defined as time between the date of the first dose of iNeo-Vac-R01 and the date of death due to any cause. 3 years after first dose of iNeo-Vac-R01
Secondary Objective Response Rate (ORR) ORR is defined as proportion of subjects with complete response (CR) and partial response (PR) to all subjects based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. 3 years after first dose of iNeo-Vac-R01
Secondary Disease Control Rate (DCR) DCR is defined as proportion of subjects with reduced or stable neoplasms that have been maintained for a certain period of time, including the proportion of subjects with CR, PR, and stable disease (SD). 3 years after first dose of iNeo-Vac-R01
Secondary Duration of Response (DOR) DOR is defined as time from first PR or CR until either disease progression or death (whichever is sooner). 3 years after first dose of iNeo-Vac-R01
Secondary Progression Free Survival (PFS) PFS is defined as time between the date of first dose of iNeo-Vac-R01 and the date of either disease progression or death (whichever is sooner). 3 years after first dose of iNeo-Vac-R01
Secondary Neoantigen-specific T Cell Response [immunogenicity] Detect the level of specific TNF-? in peripheral blood of subjects by ELISpot in order to measure the neoantigen-specific T cell response of subjects. 12 months after first dose of iNeo-Vac-R01
Secondary T Cell Subsets [immunogenicity] Detect the proportion of different T cell subsets in T cells by flow cytometry. 12 months after first dose of iNeo-Vac-R01
Secondary Cytokines Level [immunogenicity] Record the changes of IL-2, IL-6, IL-8, IL-10, IL-12, and TNF-a in peripheral blood before and after treatment. 6 months after first dose of iNeo-Vac-R01
See also
  Status Clinical Trial Phase
Recruiting NCT06019702 - Clinical Study of Personalized mRNA Vaccine Encoding Neoantigen Alone in Subjects With Advanced Digestive System Neoplasms Phase 1
Recruiting NCT06026774 - Clinical Study of Personalized mRNA Vaccine Encoding Neoantigen in Subjects With Resected Digestive System Neoplasms Phase 1
Completed NCT02909452 - Continuation Study of Entinostat in Combination With Pembrolizumab in Patients With Advanced Solid Tumors Phase 1
Active, not recruiting NCT05602935 - Efficacy and Safety of SOX Regimen Combined With Camrelizumab as Neoadjuvant Treatment in Locally Advanced Gastric Cancer: a Phase II, Single-arm Study Phase 2
Recruiting NCT04518852 - TACE, Sorafenib and PD-1 Monoclonal Antibody in the Treatment of HCC Phase 2
Completed NCT03717298 - Evaluation of Ocoxin-Viusid® in Advanced Pancreatic Adenocarcinoma Phase 2
Recruiting NCT05322486 - Palliative Primary Tumor Resection in Minimally Symptomatic Patients With Colorectal Cancer and Synchronous Unresectable Metastases
Recruiting NCT04556344 - Effectiveness of an Educational Intervention Aimed at Increasing the Emotional Competencies of Patients Under Surveillance After Antineoplastic Treatment of Oesogastric or Bronchopulmonary Cancer N/A
Terminated NCT03306693 - Educational Intervention to Increase the Emotional Competence of Patients With Oesogastric and Bronchopulmonary Cancers N/A
Active, not recruiting NCT01037049 - Optimum Timing for Surgery After Pre-operative Radiotherapy 6 vs 12 Weeks Phase 2
Recruiting NCT02208804 - Surefire Infusion System vs. Standard Microcatheter Use During Holmium-166 Radioembolization Phase 2/Phase 3
Completed NCT04080843 - Anlotinib Hydrochloride Capsules Combined With CAPEOX in RAS and BRAF Wild-type mCRC Patients Phase 2
Recruiting NCT03303495 - A Study of 2nd-line FOLFIRI ± Bevacizumab vs. Irinotecan ± Bevacizumab in mCRC Phase 3
Terminated NCT04644315 - A Home-Based Approach Study to Evaluate the Efficacy and Safety of Alectinib in Locally-Advanced or Metastatic ALK-Positive Solid Tumors Phase 2
Recruiting NCT03271255 - Apatinib Versus Bevacizumab in Second-line Therapy for Colorectal Cancer(ABST-C) Phase 2
Recruiting NCT03221335 - EUS-guided RFA for Solid Abdominal Neoplasms N/A
Recruiting NCT02487017 - DC-CIK Combined With TACE in the Treatment of Hepatocellular Carcinoma Phase 2
Not yet recruiting NCT01556815 - Sorafenib Combined With Transarterial Chemoembolization in Treating HBV-infected Patients With Intermediate Hepatocellular Carcinoma Phase 2
Recruiting NCT04949282 - Spanish Series of Patients Treated With the Radionuclide Lutetium177
Completed NCT01964430 - Nab-paclitaxel and Gemcitabine vs Gemcitabine Alone as Adjuvant Therapy for Patients With Resected Pancreatic Cancer (the "Apact" Study) Phase 3