iTAPVR Study - Phase II Randomized Study

Individualized Tumor Neoantigen Peptide Vaccine in Combination With Radiotherapy for Advanced Tumors - Phase II Randomized Study

In this study, the investigators provide an individualized tumor neoantigen peptide vaccine in combination with radiotherapy to patients with advanced malignant solid tumors. The investigators observe the post-treatment tumor burden status, the immune response induced by immune preparations, and the prolongation of patient survival time, aiming to evaluate the effectiveness and safety of the individualized tumor neoantigen peptide vaccine in combination with radiotherapy

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Tumors
• Intervention / Treatment: Other: Placebo + conventional treatment including radiotherapy; Combination product: Radiation: Radiation Therapy；Biological: Personalized tumor peptide vaccine

Detailed Description

In this study, we intend to recruit patients with advanced tumors that have failed standard treatment or progressed, and conduct a clinical study of individualized tumor neoantigen peptide vaccine combined with radiotherapy according to the process shown in the figure below: (1) for operable patients, tumor tissues were obtained surgically with peripheral blood as the control, and for inoperable patients, tumor tissues were obtained by biopsy with peripheral blood as the control, and DNA was extracted and whole exome sequencing was performed to accurately detect the tumor gene mutation. (2) Confirm the expression of the mutation in the tumor by transcriptome sequencing; (3) Analyze the HLA typing of the patient by exon sequencing results; (4) Integrate the information of mutation, gene expression and HLA typing, predict the binding ability of the mutation with HLA molecules by software, and screen the tumour neoantigen. Tumor neoantigens; in this project, for the same data, three teams will be used to perform neoantigen prediction analysis and validate each other, and the neoantigen sequence with the best solution (intersection of the three teams) will be obtained by combining the three results. (5) Synthesize tumor neoantigen peptide vaccine based on tumor neoantigen, and verify the safety of tumor neoantigen peptide vaccine by in vitro in vivo test; (6) Subjects will first receive precision radiotherapy treatment, and then enter into individualized tumor neoantigen peptide vaccine clinical trial after one week to prove the safety, feasibility and effectiveness of this combined precision therapy.

• Study Type: Interventional
• Enrollment (Estimated): 154
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yan Zhang
• Study Contact Backup: Name: Feng-Ming (Spring) Kong; Phone Number: 18807550703; Email: Kong001@hku.hk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. male or female
2. age>18 years old
3. with advanced or recurrent malignancies diagnosed by pathology and imaging, who have failed systemic standard therapy or disease progression prior to enrollment and have no effective first-line therapy (for effective therapy, refer to the latest version of the treatment guidelines published by the Chinese Society of Clinical Oncology)
4. have at least one imaging measurable lesion
5. with an expected survival of ≥ 3 months
6. with an ECOG (Eastern Cooperative Oncology Group) score of 0-2
7. have access to sufficient tumor DNA (circulating tumor DNA or tissue samples) for analysis, or have genomic/exonic/transcriptional data from tumor and normal tissues and the data meet the analysis requirements, qualified for tumor neoantigen screening, or have prepared neoantigen peptides from a certified company (GMP)
8. women of childbearing age should have negative pregnancy tests within 7 days prior to enrollment, and have no short-term plans to have children and are willing to take protective measures (contraception or other birth control methods) before and during the clinical trial
9. compliant patients who is and able to follow the study protocol and the follow-up procedures

Exclusion Criteria:

1. No neoantigens detected in the sequencing data.
2. with a history of bone marrow or stem cell transplantation
3. enrolled in other therapeutic clinical trials; clinical trials of Chinese medicine
4. with active bacterial or fungal infections
5. with active HIV (human immunodeficiency virus, human immunodeficiency virus), HCV (hepatitis C virus), HBV (hepatitis B virus), or the herpes virus (except for crusting for more than 4 weeks), or with respiratory viral infections (except for those who have been cured for more than 4 weeks)
6. with asthma, autoimmune disease, immunodeficiency
7. under treatment with immunosuppressive drugs
8. with severe coronary or cerebrovascular disease, or other conditions that concerns the investigator for enrollment
9. have clinical, psychological or social factors affecting informed consent or study implementation
10. have a history of drug or peptide allergy, or allergy to other potential immunotherapies
11. no decision making capacity for civil conduct

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Control arm: Arm #1	Other: Placebo + conventional treatment including radiotherapy; Placebo + conventional treatment including radiotherapy; Other Names: Chemical: per standard care
Experimental: Experimental arm: Arm #2; Personalized tumor peptide vaccine + conventional treatment including radiotherapy group	Combination product: Radiation: Radiation Therapy；Biological: Personalized tumor peptide vaccine; The peptide vaccine treatment will take 5 months as a treatment course until the treatment suspension event as stipulated in the plan occurred.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival	Number of participants with Adverse Events as a measure of safety and tolerability	Visits were conducted at the end (or termination) of each course and at 30, 90, and 120 days after the end of the last course for 4 months

Collaborators and Investigators

• Sponsor: The University of Hong Kong-Shenzhen Hospital
• Investigators: Principal Investigator: Clinical Cancer Center Hong Kong University Shenzhen Hospital, Municipal hospitals

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: March 10, 2024
• First Submitted That Met QC Criteria: March 10, 2024
• First Posted (Actual): March 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 10, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Neoantigen Peptide Vaccines
• Other Study ID Numbers: Neoantigen Radiotherapy

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Publications

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No