Safety and Tolerability of a mRNA Vaccine Encoding Tumor-Specific Circular RNA Antigens in Combination With Anti-PD-1 Monoclonal Antibody in Patients With Advanced Solid Tumors

NCT07245901 | Not Yet Recruiting Phase 1

• 1 other identifier: SYSKY-2025-591-02
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an Investigator-initiated, Open-Label Clinical Study of a mRNA Vaccine Encoding Tumor-Specific Circular RNA Antigens in Combination with anti-PD-1 monoclonal antibody in Patients with Advanced Solid Tumors. Preclinical studies of this project have identified that circFAM53B, which is specifically overexpressed in tumor cells, possesses the ability to encode a cryptic peptide, FAM53B-219aa, representing a potential tumor vaccine target. In this study, the sequence encoding the cryptic antigen from circFAM53B will be linearized and formulated as an mRNA vaccine (circFAM53B mRNA injection). The vaccine will be administered via lipid nanoparticle (LNP) encapsulation, and its safety and efficacy will be evaluated in combination with anti-PD-1 monoclonal antibody therapy.

Conditions

Solid Tumor

Keywords

Tumor vaccine; mRNA vaccine; solid tumor; immunotherapy

Outcome Measures

Primary Outcomes (3)

• Safety and Tolerability

  Safety and tolerability as determined by assessment of dose limiting toxicities and the maximum tolerated dose or maximal assessed dose per protocol of the vaccine with cancers.

  12 months

• Recommended Phase 2 Dose (RP2D)

  To determine a recommended phase 2 dose of the vaccine for further development by evaluating number of patients with treatment-related adverse events as assessed by the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0)

  12 months

• Maximum Tolerated Dose (MTD)

  Determine the maximum tolerated dose by assessing the Incidence of Dose Limiting Toxicities (DLTs), treatment emergent and treatment related adverse events (assessed by CTCAE v5.0).

  12 months

Secondary Outcomes (4)

• Overall Response Rate (ORR): Number of Participants with Tumor Response (Partial or Complete)

  Baseline through disease progression by Response Evaluation Criteria of Solid Tumors Version 1.1 (RECIST 1.1), start of new anti-cancer therapy, withdrawal of consent, death and last safety follow-up visit (up to approximately 3 years)

• Duration of Response (DoR)

  Baseline through disease progression by RECIST 1.1, start of new anti-cancer therapy, withdrawal of consent, death and last safety follow-up visit (up to approximately 3 years)

• Progression Free Survival (PFS)

  Baseline through disease progression by RECIST 1.1, start of new anti-cancer therapy, withdrawal of consent, death and last safety follow-up visit (up to approximately 3 years)

• Overall Survival (OS)

  Baseline to death of any cause (up to approximately 3 years)

Study Arms (2)

Dose Escalation phase

EXPERIMENTAL

A single dose of the PD-1 monoclonal antibody will be administered first, followed by combination treatment with the mRNA vaccine and the PD-1 antibody 21 days later. Participants will receive circFAM53B mRNA injection via an intramuscular (IM) injection on Day 1 of each 21-day cycle for up to 9 cycles, combined with PD-1 monoclonal antibody therapy for up to 35 cycles.

Drug: circFAM53B mRNA vaccine; Drug: toripalimab

Dose Expansion phase

EXPERIMENTAL

A single dose of the PD-1 monoclonal antibody will be administered first, followed by combination treatment with the mRNA vaccine and the PD-1 antibody 21 days later. Participants will receive circFAM53B mRNA injection via an intramuscular (IM) injection on Day 1 of each 21-day cycle for up to 9 cycles, combined with PD-1 monoclonal antibody therapy for up to 35 cycles.

Drug: circFAM53B mRNA vaccine; Drug: toripalimab

Interventions

circFAM53B mRNA vaccine DRUG

IM injection on Day 1 of each 21-day cycle for up to 9 cycles

Also known as: circFAM53B mRNA injection

Dose Escalation phase; Dose Expansion phase

toripalimab DRUG

Intravenous infusion once every 21 days

Also known as: anti-PD-1 monoclonal antibody

Dose Escalation phase; Dose Expansion phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary participation: The patient voluntarily agrees to participate in the study, signs a written informed consent form (ICF), and is willing and able to comply with the study protocol requirements.
• Age and sex: Male or female patients aged ≥18 years.
• Life expectancy: Expected survival of ≥3 months.
• Diagnosis: Histologically or cytologically confirmed unresectable or metastatic advanced solid malignancies, including but not limited to pancreatic cancer, breast cancer, non-small cell lung cancer, melanoma, and colorectal cancer.
• Tumor tissue availability: Patients must have adequate fresh tumor tissue obtained via biopsy or surgery prior to treatment, or available formalin-fixed paraffin-embedded (FFPE) samples. The expression of circFAM53B-219aa in the specimen must be confirmed by RT-qPCR analysis and/or immunohistochemistry.
• HLA genotyping will be performed using peripheral blood samples, employing polymerase chain reaction-sequence-based typing (PCR-SBT) combined with Sanger sequencing, with allele assignment referenced to the IMGT/HLA database, or alternatively, using PCR with sequence-specific oligonucleotide (SSO) probes, sequence-specific primers (SSP), or next-generation sequencing (NGS) technologies. Subsequently, NetMHCpan and MHCflurry predictive models will be applied to identify tumor-specific circFAM53B-39aa-derived peptides that bind to HLA class I molecules (HLA-A, -B, and -C) and to evaluate their binding affinity. Patients with HLA genotypes showing a predicted binding rank value \<2 will be eligible for enrollment.
• Measurable disease: At least one measurable lesion or bone-only lesion as defined by RECIST v1.1 (see Appendix 4: Response Evaluation Criteria in Solid Tumors).
• Prior therapy: Patients who have failed standard therapy, have no available standard treatment, or cannot tolerate standard treatment-related toxicities.
• Performance status: ECOG performance status 0-2.
• Adequate organ function as defined below:
• Hematology:
• Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;
• Platelet count (PLT) ≥ 75 × 10⁹/L;
• Hemoglobin (Hb) ≥ 90 g/L.
• Hepatic function:

You may not qualify if:

• Participants meeting any of the following criteria will be excluded from the study:
• Active infection requiring systemic therapy.
• Uncontrolled tumor-associated pain, as determined by the investigator. Patients requiring analgesic therapy must be on a stable pain management regimen prior to enrollment. Symptomatic lesions amenable to palliative radiotherapy should be treated before study entry.
• Severe cardiac disease or cardiac dysfunction expected to preclude tolerance to treatment, including but not limited to: life-threatening arrhythmias or high-grade atrioventricular block, unstable angina, clinically significant valvular heart disease, electrocardiographic evidence of transmural myocardial infarction, or uncontrolled hypertension.
• Receipt of radiotherapy, chemotherapy, or endocrine therapy within 4 weeks prior to enrollment, or current participation in another interventional clinical trial.
• Pregnant or breastfeeding women.
• Active autoimmune disease, a history of autoimmune disease, or conditions requiring systemic corticosteroids or immunosuppressive therapy (\>10 mg/day prednisone or equivalent).
• Exceptions: hormone replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroid replacement for adrenal or pituitary insufficiency) is permitted.
• History of congenital or acquired immunodeficiency, including HIV seropositivity.
• Active tuberculosis (TB) infection within 1 year prior to enrollment, or a history of active TB infection more than 1 year ago that was not adequately treated.
• Active hepatitis B or C infection.
• Patients who are HBsAg or HBcAb positive may be enrolled if HBV DNA is below the lower limit of normal (LLN) at the study site.
• Patients who are HCV antibody positive may be enrolled if HCV RNA is below the LLN at the study site.
• Carriers participating in the study should receive antiviral therapy as appropriate, with periodic quantitative nucleic acid testing during the study.
• Active syphilis.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead
• Zenith Institute of Medical Sciences, Guangzhou: collaborator

MeSH Terms

Interventions

toripalimab; spartalizumab

Study Officials

• Erwei Song

  Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

  STUDY CHAIR

Central Study Contacts

Huang Di

CONTACT

0086-020-8133 2199; huangd63@mail.sysu.edu.cn

Xiangyu Meng

CONTACT

0086-020-8133 2199; mengxy55@mail2.sysu.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Ph.D

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: November 24, 2025
• Study Start: December 5, 2025
• Primary Completion (Estimated): December 5, 2028
• Study Completion (Estimated): December 5, 2030
• Last Updated: November 24, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share