A Phase I/ II Study of Fragmented Autoantigen Stimulated T-cell-immunotherapy Combined with Radiotherapy (FAST-CR) (FAST-CR)

Evaluation and exploration of the phase I/II clinical safety and efficacy of personalized FAST(Radiation fueled antigens stimulated T-cell immunotherapy )cancer vaccine combined with radiotherapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Melanoma; Lung Cancer; Breast Cancer, Colorectal Cancer
• Intervention / Treatment: Biological: individualized tumor FAST vaccine combination (including adjuvant)

Detailed Description

Tumor whole-cell vaccines, as one of the methods for tumor immunotherapy, have become a key focus of numerous preclinical studies. Among these, the latest approaches include cryopreserved silica-based vaccines/aged cell vaccines and genetically engineered vaccines. These vaccines induce immunogenic cell death in tumor cells, thereby reshaping the body's immune tolerance and promoting in-situ immunity (in-situ vaccination). They enhance the diversity of tumor-associated antigens in the draining lymph nodes, increase the recruitment of T cells, and promote tumor recognition and anti-tumor effects. At the same time, whole-cell vaccines retain all potential antigens of the tumor cells, and this integrity increases the likelihood of immune activation and recognition of distal tumors. Additionally, since the vaccine uses the patient's own tumor tissue, it reduces the risk of immune overactivation that might be caused by foreign components. Preclinical studies have found that in a surgical resection model of primary tumors in experimental animals, the FAST vaccine can significantly inhibit the recurrence and metastasis of tumor lesions, remodel the immune microenvironment of colonized organs, achieve systemic clearance of micro-metastases, suppress tumor recurrence and metastatic progression, and prolong the survival of the experimental animals. On the other hand, many advanced cancer patients in the clinic are not amenable to surgical resection, with a high tumor burden. Moreover, the immune response induced by the whole-cell autologous FAST vaccine requires a certain period to develop. Therefore, in our preclinical study, the investigators combined FAST vaccine administration with radiotherapy to control local tumors in experimental animals. The results showed that this approach significantly enhanced both innate and adaptive immunity, inhibited tumor progression and metastasis, and improved the survival rate of the experimental animals.

This study aims to recruit tumor patients who have undergone standard surgical treatment and those with advanced tumors who have failed standard treatment or experienced disease progression (after failure of third-line treatment),Using the patient's individualized tumor tissue, the investigators will prepare the FAST tumor cell vaccine and combine it with precision radiotherapy to conduct safety and efficacy studies on tumor patients who meet the inclusion criteria.

• Study Type: Interventional
• Enrollment (Estimated): 154
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Feng-Ming (Spring) Kong; Phone Number: +86 18807550703; Email: kong0001@hku.hk
• Study Contact Backup: Name: Gen Yang; Phone Number: +86 15010272716

Participation Criteria

Eligibility Criteria

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

Study Population

Patients who have undergone standard surgical treatment and are planned to be enrolled for controlling recurrence/metastasis of tumors.

Pathological and radiological diagnosis of advanced (failed after third-line treatment) or recurrent malignant tumors. Prior to enrollment, these patients have received systemic standard treatment that has failed or the disease has progressed, and currently, there are no effective first-line treatment options for advanced tumors (effective treatment options are based on the latest clinical treatment guidelines published by the Chinese Society of Clinical Oncology).

Description

Inclusion Criteria:

- Voluntarily agree to participate in this study. Age: 18-80 years, regardless of gender. Pathological and imaging diagnosis of advanced or recurrent malignant tumors. The patient must have previously received systemic standard treatment that has failed or led to disease progression, with no effective first-line treatment options available for advanced tumors (effective treatment options refer to the latest clinical guidelines published by the "Chinese Society of Clinical Oncology"). Alternatively, the patient may have undergone standard surgical treatment for tumor relapse prevention.

At least one measurable lesion on imaging (excluding patients who have undergone surgical treatment).

Expected survival ≥ 6 months. ECOG (Eastern Cooperative Oncology Group) performance status score of 0-1. No infectious diseases: HIV antibody negative. Normal hematological function: White blood cells ≥ 3000 cells/µL, hemoglobin ≥ 9 g/dL, platelets ≥ 75,000 cells/µL, absolute neutrophil count > 1000 cells/mm³.

Normal renal function: Serum creatinine (Cr) ≤ ULN × 1.5. Normal liver function: Serum ALT/AST levels less than three times the upper limit of normal.

The patient must be willing to sign an informed consent form and able to comply with the treatment plan.

The patient must undergo tumor resection or biopsy (for vaccine preparation) and peripheral blood collection (for efficacy and prognosis evaluation).

Exclusion Criteria:

- Patients who do not have enough tumor resected or puncture tissue for vaccine production.

Patients who have failed third-line therapy, and whose tumor location or type is not suitable for radiotherapy (as evaluated by the expert group).

Patients whose tumor tissue preparation for the vaccine does not meet the efficacy assessment criteria before enrollment (individualized FAST vaccine Elispot test, see Appendix 4 for specific testing protocol).

Patients with a history of bone marrow or stem cell transplantation. Patients currently participating in other therapeutic clinical trials; Traditional Chinese medicine clinical trials.

Patients with active bacterial or fungal infections as per NCI-CTC (National Cancer Institute Common Terminology Criteria for Adverse Events) CTCAE 5.0.

Patients infected with HIV (Human Immunodeficiency Virus), HCV (Hepatitis C Virus), HBV (Hepatitis B Virus), severe asthma, autoimmune diseases, immunodeficiency, or those undergoing immunosuppressive therapy.

Patients with herpesvirus infection (except those whose lesions have scabbed for more than 4 weeks).

Patients with respiratory viral infections (except those who have been cured for more than 4 weeks).

Patients with severe coronary artery or cerebrovascular diseases, or other diseases that the investigator considers should be excluded.

Patients with clinical, psychological, or social factors that affect their ability to provide informed consent for the study.

Patients with a history of autoimmune diseases, such as but not limited to inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis. Patients with autoimmune-related thyroid diseases and vitiligo are allowed.

Patients with severe chronic or acute comorbidities, such as heart disease (NYHA Class III or IV), liver disease, or other diseases that the principal investigator considers to pose unnecessary high risk in relation to the study drug treatment.

Patients who have a second malignant tumor at the same time (or within the past 5 years), except for melanoma skin cancer, cervical carcinoma in situ, controlled superficial bladder cancer, or other treated carcinoma in situ.

Patients with active acute or chronic infections, including urinary tract infections, HIV (as confirmed by ELISA and Western Blot). HIV-infected individuals may be excluded because immunosuppression could prevent them from responding to the vaccine; chronic hepatitis patients may be excluded due to concerns that vaccination could exacerbate their hepatitis.

Patients with a history of drug or peptide allergies, or allergies to other potential immunotherapies.

Patients undergoing chronic steroid treatment (or other immunosuppressive agents, such as azathioprine or cyclosporine A) will be excluded due to potential immunosuppression. Patients must stop any steroid treatment 6 weeks prior to enrollment (except for drugs used for chemotherapy, contrast-enhanced imaging, or acute treatment of complications such as gout attacks <5 days).

Patients with acute or chronic skin diseases will be excluded, as these conditions could affect the injection into the skin of the limbs or the subsequent evaluation of potential skin reactions.

Patients without legal capacity.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: standard treatment + adjuvant; Patients in the control group include two categories: (1) surgical patients who receive standard postoperative treatment according to guidelines, and (2) non-surgical patients who receive standard RT.
Experimental: Standard treatment + individualized tumor FAST vaccine combination (including adjuvant); Surgical Patients: These patients will receive standard postoperative treatment according to guidelines. In Phase I of the trial, they will be randomly administered the aforementioned low, medium, or high doses of the FAST vaccine (P12). In Phase II, the optimal dose will be selected for each patient (as assessed by an expert panel). Non-Surgical Patients: Before starting the tumor vaccine, these patients will first undergo three sessions of precision radiotherapy (the doctor will determine whether the patient should receive 2 Gy × 3 or 8 Gy × 3, depending on the patient's condition). After completing the radiotherapy, the individualized tumor vaccine will be administered one week later. Similarly, in Phase I, these patients will receive the low, medium, or high doses of the FAST vaccine (P12) in a randomized manner. In Phase II, the optimal dose will be selected for each patient (as assessed by the expert panel). Tumor vaccine treatment will be administered in cycles of 5	Biological: individualized tumor FAST vaccine combination (including adjuvant); Using the patient's individual tumor tissue, an autologous FAST (Fragmented Autoantigen Stimulated T-cell Immunotherapy) vaccine is prepared.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
safe	The primary endpoint of this study: The Phase I safety evaluation will involve a 3×3 dose escalation of the vaccine (based on a similar international clinical trial, NCT05366062, with low, medium, and high-dose groups, each group receiving 500,000, 1 million, and 2 million cancer cell fragments, respectively, with 3 participants per group). The safety profile will be summarized, including the incidence and severity of adverse events (Evaluation criteria: Treatment toxicity graded according to CTCAE 5, (Common Terminology Criteria for Adverse Events version 5). If the summary of Phase I toxicity shows no significant higher toxicity compared to existing immunotherapies, the study will proceed to the Phase II efficacy trial.	one month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
OS (Overall Survival)	OS (Overall Survival) is defined as the time from the start of FAST treatment to death from any cause.	5 years
DFS (disease free survival)	the period of time from the end of treatment or the initial diagnosis of the disease during which the patient shows no signs of disease recurrence, metastasis, or the appearance of new tumors. It is commonly used to assess the disease-free period following cancer treatment.	5 years

Collaborators and Investigators

• Sponsor: Fengming Kong
• Collaborators: Peking University; The University of Hong Kong-Shenzhen Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 25, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: December 31, 2024
• First Submitted That Met QC Criteria: December 31, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 7, 2025
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: tumor vaccine; TCV; immunogenic cell death
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: GCOG0052

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
• product manufactured in and exported from the U.S.: No