A Study of RNA Tumor Vaccine in Patients With Advanced Solid Tumors

A Single-Arm, Open-Label, Exploratory Study to Evaluate the Safety of RNA Tumor Vaccine Injection Alone/in Combination With PD-1 Inhibitor in the Treatment of Advanced Solid Tumors With KRAS Mutation

This is a single-arm, open-label, clinical pharmacology study to evaluate the safety of RNA tumor vaccine injection alone/in combination with PD-1 inhibitor in the treatment of advanced solid tumors with KRAS mutation.

The purpose of this study is to evaluate the safety and tolerability, antitumor activity, The immunoreactivity, pharmacokinetics and of RNA tumor vaccine.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor
• Intervention / Treatment: Biological: RNA tumor vaccine; Biological: RNA tumor vaccine+Navuliumab

Detailed Description

This is an investigator initiated , sinle-arm, open-label clinical pharmacology to evaluate the safety and efficacy of RNA vaccine injection alone/in combination with PD-1 inhibitor in patients with advanced solid tumors with KRAS mutation (G12C, G12D, or G12V) and HLA type HLA-A11:01 or HLA C08:02. 10 subjects were enrolled. Monotherapy and combination therapy are included. Some eligible subjects will receive single drug therapy with RNA tumor vaccine injection, and some will receive combined treatment with PD-1. Among them:

Arm A:RNA tumor vaccine The single-agent study evaluated the safety, efficacy and pharmacokinetic characteristics of a fixed-dose (600ng) KRAS-targeted RNA vaccine injection as a single agent in humans. Eligible subjects will receive a single dose of RNA vaccine injection on day 1, day 4, day 7, and day 14, each dose of 600ng.

Arm B: RNA tumor vaccine+Navuliumab Subjects will receive maintenance therapy with a PD-1 inhibitor in addition to monotherapy with the RNA tumor vaccine injection. Subjects received a single dose of RNA vaccine injection on day 1, day 4, day 7, and day 14, with each dose of 600 ng. Inhibitors, accept the Navuliumab on day 14, the recommended dose is 3 mg/kg, intravenous injection every 2 weeks.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Zhou huan, MD; Phone Number: 13665527160; Email: zhouhuanbest@163.com

Study Locations

• China
  • Anhui
    • Bengbu, Anhui, China, 233030
      • Recruiting
      • First Affiliated Hospital Bengbu Medical College
      • Contact: Zhou huan, MD; Phone Number: 13665527160; Email: zhouhuanbest@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. The patient is at least 18 years old with no gender limitation;
2. Patients with advanced malignant solid tumors confirmed by histopathology or cytology and failed to receive standard treatment or without standard treatment;
3. Identification of at least one KRAS mutation: G12C, G12D or G12V;
4. The subtype was identified as HLA-A11:01 or C08:02;
5. Have at least one measurable lesion according to RECIST V1.1;
6. ECOG PS score was 0-2 in the Eastern Oncology Group;
7. Full organ and bone marrow function, as defined below:
8. Sign written informed consent and be able to comply with the visits and related procedures specified in the program;
9. Eligible fertile patients (male and female) must agree to use a reliable contraceptive method (hormonal or barrier methods or abstinence) during the study period;

Exclusion Criteria:

1. A history of severe allergy to biological products;
2. Those in pregnancy or lactation;
3. The expected survival time is less than 3 months;
4. Those who have undergone major surgery within 4 weeks prior to signing the informed consent, or who plan to undergo major surgery during the study period;
5. Received chemotherapy, biotherapy, endocrine therapy, immunotherapy and other anti-tumor drugs within 2 weeks before the first administration;
6. Participating in other clinical studies;
7. Patients with central nervous system metastasis or a history of central nervous system metastasis;
8. Adverse effects of previous antitumor therapy have not recovered to NCI CTCAE V5.0 rating ≤1 (except hair loss);
9. Serious cardiovascular and cerebrovascular diseases, hypertension that is still poorly controlled after standard treatment (systolic blood pressure > 150mmHg, diastolic blood pressure > 90mmHg);
10. Patients with active ulcers and gastrointestinal bleeding;
11. Patients with uncontrollable pleural effusion, abdominal effusion and pericardial effusion;
12. Active infection requiring treatment;
13. HIV, HCV, syphilis, CMV, EBV infected patients; Patients with active HBV replication;
14. A history of interstitial lung disease;
15. The patient has an autoimmune disease or is in an immunosuppressed state; Current systemic steroid use (except recent or current inhaled steroid use);
16. Other conditions that the investigator assessed as ineligible for inclusion.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Drug: RNA tumor vaccine Administration: intramuscular injection Dose: 600 ng/ time Dosing cycle: Day 1, day 4, day 7, and day 14.	Biological: RNA tumor vaccine; Subjects will receive single dose of RNA tumor vaccine injection on day 1, day 4, day 7, and day 14, each dose of 600 ng.
Experimental: Arm B; Drug: RNA tumor vaccine+Navuliumab Administration: intravenous injection Dose: 3 mg/kg Timing of administration: Administration was initiated 14 days after the first intramuscular injection of the RNA tumor vaccine. Duration of administration: once every 2 weeks.	Biological: RNA tumor vaccine+Navuliumab; RNA tumor vaccine+Navuliumab Subjects will receive maintenance therapy with a PD-1 inhibitor in addition to monotherapy with the RNA tumor vaccine injection. Subjects received a single dose of RNA vaccine injection on day 1, day 4, day 7, and day 14, with each dose of 600 ng. Inhibitors, accept the Navuliumab on day 14, the recommended dose is 3 mg/kg, intravenous injection every 2 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Graded according to the NCI CTCAE version 5.0.	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the antitumor activity	To assess per RECIST and iRECIST	Up to 2 years
The changes of the immunoreactivity during treatment.	Peripheral blood T lymphocyte subtype	Up to 28 Days

Collaborators and Investigators

• Sponsor: First Affiliated Hospital Bengbu Medical College

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2022
• Primary Completion (Anticipated): January 19, 2023
• Study Completion (Anticipated): January 19, 2024

Study Registration Dates

• First Submitted: January 19, 2022
• First Submitted That Met QC Criteria: January 19, 2022
• First Posted (Actual): January 21, 2022

Study Record Updates

• Last Update Posted (Actual): March 23, 2022
• Last Update Submitted That Met QC Criteria: March 21, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: immunotherapy; PD-1; KRAS mutation; Advanced Solid Tumor; injection; RNA tumor vaccine
• Additional Relevant MeSH Terms: Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: LWY21084CBY

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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