Exploratory Clinical Study of FAP mRNA Vaccine in Patients With Advanced Malignant Solid Tumors

An Exploratory Basket Study on The Application of Therapeutic mRNA Vaccine Targeting FAP in Advanced Malignant Solid Tumors

Cancer-associated fibroblasts (CAFs), as core regulators within the tumor microenvironment, significantly impede the intratumoral penetration of therapeutic agents and suppress the effective infiltration and activation of immune cells by constructing elaborate physical and functional barriers. Fibroblast activation protein (FAP) is a highly specific therapeutic target for CAFs, owing to its nearly tumor-restricted expression profile. Therefore, developing therapeutic strategies that specifically target FAP to eliminate CAFs and subsequently remodel the tumor microenvironment may effectively disrupt the multi-dimensional defense system established by CAFs, thereby significantly enhancing the delivery efficiency of anti-tumor agents and improving responsiveness to immunotherapy.

This Phase I clinical trial aims to evaluate the safety, tolerability, pharmacokinetics, immunogenicity, and preliminary antitumor activity of FAP mRNA Vaccine combined with immune checkpoint inhibitors in patients with advanced malignant solid tumors.

Study Overview

• Status: Not yet recruiting
• Conditions: Advanced Malignant Solid Tumors
• Intervention / Treatment: Biological: FAP mRNA vaccine (dose 1) + immune checkpoint inhibitors; Biological: FAP mRNA vaccine (dose 2) + immune checkpoint inhibitors; Biological: FAP mRNA vaccine (dose 3) + immune checkpoint inhibitors; Biological: FAP mRNA vaccine (dose 4) + immune checkpoint inhibitors

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

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• 1. Male or female patients: aged ≥ 18 years old;
• 2. Patients with histopathologically confirmed advanced malignant solid tumors (such as patients with advanced lung cancer, advanced colorectal cancer, advanced pancreatic carcinoma, etc.);
• 3. Patients refractory or intolerant to standard clinical treatment regimens;
• 4. According to the RECIST 1.1 criteria, at least one measurable lesion is required;
• 5. Eastern Cooperative Oncology Group (ECOG) performance status score: 0 - 1;
• 6. Expected survival time ≥ 3 months;
• 7. Main organ functions are in good condition;
• 8. Participants must have no plans for pregnancy during the treatment period and agree to use effective contraception voluntarily throughout the study period and for four months after discontinuation of treatment;
• 9. Sign a written informed consent form;
• 10. Ability to communicate effectively with the research team and willingness to comply fully with all protocol-specified requirements.

Exclusion Criteria:

• 1. History of other malignancies, except for adequately treated and non-recurrent within 5 years prior to screening basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, cervical carcinoma in situ, or gastrointestinal mucosal carcinoma, which the investigator deems eligible for inclusion;
• 2. Known central nervous system (CNS) metastases that are untreated or not effectively controlled by prior therapy;
• 3. Patients with serious cavity effusion;
• 4. Patient has comorbid conditions associated with elevated FAP expression beyond solid tumors, including pulmonary fibrosis, liver fibrosis, renal fibrosis, and rheumatoid arthritis, etc.;
• 5. Patients with uncontrolled cardiac clinical symptoms or diseases, such as heart failure of NYHA class II or above, unstable angina pectoris, having had a myocardial infarction within six months, and having clinically significant supraventricular or ventricular arrhythmias that require treatment or intervention;
• 6. A history of thrombotic events (arterial or venous) within 6 months prior to enrollment, such as deep vein thrombosis, and pulmonary embolism;
• 7. Any active autoimmune disease or history of autoimmune diseases, including but not limited to: neurologic diseases related to immunity, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barré syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), connective tissue disorders, scleroderma, inflammatory bowel disease (including Crohn's disease and ulcerative colitis), autoimmune hepatitis, toxic epidermal necrolysis (TEN), or Stevens-Johnson syndrome (excluding type 1 diabetes mellitus controlled with stable-dose insulin);
• 8. According to the investigator's judgment, there are concomitant uncontrolled diseases that may seriously endanger patient safety or affect the patient's completion of the study;
• 9. A known history of interstitial pneumonia or highly suspected interstitial pneumonia; or patients with lung abnormalities that could interfere with the detection or management of suspected drug-related pulmonary toxicity during the study;
• 10. Known allergy to the investigational drug (including any excipients). A history of severe allergic reactions to any drugs, foods, or vaccines, such as anaphylactic shock, allergic laryngeal edema, allergic dyspnea, allergic purpura, thrombocytopenic purpura, localized allergic necrotic reactions (Arthus reaction), etc.;
• 11. The last anti-cancer treatment occurred less than 4 weeks before the first vaccination; patients with unresolved treatment-related adverse effects (except hair loss) from previous anti-cancer treatments;
• 12. Patients who have previously received treatment with immune checkpoint inhibitors and experienced immune-related adverse events graded ≥3 according to the NCI CTCAE criteria;
• 13. Systemic treatment with corticosteroids (>10 mg/day of prednisone or equivalent doses of other glucocorticoids) or other immunosuppressive agents within 14 days before the first dose of the vaccine. However, the following situations are allowed: In the absence of active autoimmune disease, inhaled or local use of corticosteroids or adrenal hormone replacement with <=10 mg/day prednisone is allowed;
• 14. Received mRNA vaccines or lipid nanoparticles (LNP) or equivalent nanoparticle delivery drugs within 6 months prior to the first dose of the vaccine;
• 15. Previously received live attenuated vaccine/inactivated vaccine within 6 months;
• 16. Previous organ transplantation or allogeneic hematopoietic stem cell transplantation;
• 17. Blood donation or significant blood loss (>450 mL) within 3 months prior to screening;
• 18. Major surgery within 4 weeks prior to screening (small surgeries such as catheter placement, biopsy required by the protocol, etc., are not exclusion criteria), or the surgical or traumatic effects have not been resolved within 14 days before enrollment;
• 19. A history of drug abuse or known medical, psychological, or social conditions, such as a history of alcoholism or drug abuse;
• 20. Human immunodeficiency virus (HIV) positive, or positive for syphilis antibodies; patients with active HBV infection, or HCV infection;
• 21. Patients with active tuberculosis (TB) or a history of active TB; or those requiring systemic treatment for severe acute or chronic infections
• 22. Pregnant or breastfeeding women;
• 23. Any other factors that the investigator believes may make the patient unsuitable for participation in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FAP mRNA vaccine, Dose 1; FAP mRNA vaccine	Biological: FAP mRNA vaccine (dose 1) + immune checkpoint inhibitors; FAP mRNA vaccine (dose 1) in combination with immune checkpoint inhibitors treatment
Experimental: FAP mRNA vaccine, Dose 2; FAP mRNA vaccine	Biological: FAP mRNA vaccine (dose 2) + immune checkpoint inhibitors; FAP mRNA vaccine (dose 2) in combination with immune checkpoint inhibitors treatment
Experimental: FAP mRNA vaccine, Dose 3	Biological: FAP mRNA vaccine (dose 3) + immune checkpoint inhibitors; FAP mRNA vaccine (dose 3) in combination with immune checkpoint inhibitors treatment
Experimental: FAP mRNA vaccine, Dose 4	Biological: FAP mRNA vaccine (dose 4) + immune checkpoint inhibitors; FAP mRNA vaccine (dose 4) in combination with immune checkpoint inhibitors treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety: Type, frequency, and severity of treatment-related adverse events as assessed by CTCAE V5.0	During one year after initial treatment
Dose-limiting toxicities (DLTs) and their incidence rates	During one year after initial treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Objective response rate (ORR)	During one year after initial treatment
Disease control rate (DCR)	During one year after initial treatment
Progression-free survival (PFS)	During one year after initial treatment
Immunogenicity: Specific T cell levels targeting FAP antigen	During one year after initial treatment

Collaborators and Investigators

• Sponsor: West China Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): January 25, 2026
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: January 12, 2026
• First Submitted That Met QC Criteria: January 22, 2026
• First Posted (Actual): January 23, 2026

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 22, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Immune Checkpoint Inhibitors
• Other Study ID Numbers: 2025-2148

Drug and device information, study documents

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