A Single Arm Clinical Study of Dendritic Cell Vaccine Loaded With Circular RNA Encoding Cryptic Peptide for Patients With HER2-negative Advanced Breast Cancer

NCT06530082 | Not Yet Recruiting Phase 1

• 1 other identifier: 202402
• Study Type: interventional
• Target: 48
• Locations: 0 countries
• Sites: N/A

Brief Summary

The purpose of this clinical trial is to understand the safety and tolerability of CircFAM53B-219aa DC vaccine monotherapy and its combination with camrelizumab in the treatment of HER2-negative advanced breast cancer, as well as to evaluate its efficacy.

Conditions

Breast Neoplasms

Outcome Measures

Primary Outcomes (2)

• Incidence of Dose-Limiting Toxicity (DLT)

  DLT (Dose-Limiting Toxicity) is defined as the following adverse events occurring during the first cycle (21 days) of treatment with the CircFAM53B-219aa DC vaccine, and deemed related to the study vaccine by the investigator. Any adverse event resulting in death, for which it is unclear if it is due to the study disease, pre-existing conditions, new complications, or unrelated to treatment, is also considered a DLT.

  From the vaccine up to 21 days post-injection

• Incidence of Grade≥3 Treatment-Emergent Adverse Event (TEAE)

  Adverse events are reported based upon CTCAE version 5.0 criteria. The incidence of Grade≥3 TEAE occurring within the 21 days immediately after DC vaccine will be summarized with descriptive statistics.

  From the vaccine up to 21 days post-injection

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  Up to approximately two years

• Overall Survival (OS)

  Up to approximately two years

• Progression Free Survival (PFS)

  Up to approximately two years

Study Arms (2)

CircFam53B-219aa DC vaccine

EXPERIMENTAL

Subjects enrolled in the dose-escalation phase will receive CircFam53B-219aa DC vaccine once every 3 weeks according to the study protocol. Evaluations will be conducted every 6 weeks. If the investigator deems that the subject is deriving clinical benefit and with the subject's consent, additional vaccinations may be administered until unacceptable toxicity occurs, consent is withdrawn, or disease progression is observed.

Biological: CircFam53B-219aa DC vaccine

CircFam53B-219aa DC vaccine+camrelizumab

EXPERIMENTAL

Subjects enrolled in the sample size expansion phase will receive CircFam53B-219aa DC vaccine combined with camrelizumab once every 3 weeks. Evaluations will be conducted every 6 weeks. If the investigator deems that the subject is deriving clinical benefit and with the subject's consent, additional vaccinations may be administered until unacceptable toxicity occurs, consent is withdrawn, or disease progression is observed.

Biological: CircFam53B-219aa DC vaccine; Drug: camrelizumab

Interventions

CircFam53B-219aa DC vaccine BIOLOGICAL

Dendritic cell vaccine loaded with circular RNA-encoded cryptic peptide. Administer intradermally once every 3 weeks according to a dose-escalation gradient of 0.5-1×10⁷, 1.5-2×10⁷, and 4-5×10⁷ cells.

CircFam53B-219aa DC vaccine; CircFam53B-219aa DC vaccine+camrelizumab

camrelizumab DRUG

Camrelizumab for Injection, 200 mg IV infusion, administered once every 3 weeks.

CircFam53B-219aa DC vaccine+camrelizumab

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• In order to be eligible for participation in this trial, the participant must:
• Have voluntarily joined the study, signed the informed consent form, and be willing and able to comply with the study protocol.
• Be a female aged 18 to 70 years (calculated on the day of signing the informed consent).
• Have been diagnosed with unresectable locally advanced or recurrent, metastatic breast cancer (stage IIIB/C or IV), HER2-negative (diagnosed according to the latest ASCO CAP guidelines), with the disease in a stable or progressive state.
• Have triple-negative breast cancer with disease progression or intolerance to prior first-line chemotherapy, or ER and/or PgR-positive breast cancer with failure in at least one line of endocrine or CDK4/6 inhibitor therapy.
• Have HLA-A\*02:01 genotype (detected by peripheral blood extraction using PCR-SBT and Sanger sequencing, and typed with reference to the IMGT/HLA database).
• Have a positive FAM53B-219aa IHC test result in tumor biopsy specimens.
• Have not received any previous cell infusion therapy or tumor vaccine treatment.
• Have had adequate washout from previous antitumor treatments: no anti-angiogenesis drugs within 4 weeks, no chemotherapy or targeted therapy within 3 weeks, no radiotherapy within 2 weeks, and no endocrine therapy within 1 week. For the sample size expansion phase, if the immune checkpoint inhibitors to be used in this study were used in prior (neo)adjuvant treatment, at least 12 months must have elapsed before enrollment in this study.
• Have at least one measurable lesion as defined by RECIST v1.1. If the lesion has received prior radiotherapy, it must have shown definite disease progression post-radiotherapy to be considered measurable.
• Have accessible recent tumor tissue from the breast cancer lesion (unresectable locally advanced or recurrent, metastatic breast cancer lesion) to determine breast cancer molecular typing and PD-L1 expression levels, unless inaccessible or unsafe to obtain.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
• Have an expected survival time of ≥12 weeks.
• Have adequate function of major organs meeting the following requirements (use of any blood components and cell growth factors is not allowed within 14 days before surgery):
• a) Complete Blood Count test:

You may not qualify if:

• The participant must be excluded from participating in this trial if the participant:
• Has rapidly progressing breast cancer as determined by the investigator.
• Has active central nervous system metastases or carcinomatous meningitis (except stable brain metastases, those deemed not requiring medication within 2 weeks by clinical judgment, or those not dependent on hormones). Stable brain metastases that have been treated must provide at least two brain imaging assessments: (i) after completion of brain metastasis treatment, and (ii) at the screening period of this study (with a minimum of 4 weeks from (i)).
• Has spinal cord compression that has not been relieved by surgery and/or radiotherapy (patients whose symptoms have improved for ≥1 week before surgical sampling can be included).
• Has uncontrolled pleural effusion, pericardial effusion, or ascites (patients with indwelling catheters are allowed to participate).
• Has uncontrollable tumor-related pain as determined by the investigator. Participants requiring analgesic treatment must have a stable pain management plan before enrollment, and symptomatic lesions suitable for palliative radiotherapy should be treated before enrollment.
• Has a history of malignancy other than the target indications within the last 5 years (exceptions include: adequately treated basal cell carcinoma or squamous cell carcinoma of the skin, and ductal carcinoma in situ of the breast after radical surgery).
• Has a significant history of cardiovascular disease, including but not limited to: (1) congestive heart failure (NYHA classification \>2); (2) unstable angina; (3) myocardial infarction within the past 3 months; (4) any supraventricular or ventricular arrhythmia requiring treatment or intervention.
• Has interstitial pneumonia or clinically significant active pneumonia at screening, or other respiratory diseases that seriously affect pulmonary function.
• Has an active infection requiring systemic antibiotic therapy (local use of antibiotics excluded) or has unexplained fever \>38.5℃ at screening, excluding fever due to cancer.
• Has had arterial and/or venous thrombotic events within the past 5 months, such as cerebrovascular accident, deep vein thrombosis, or pulmonary embolism.
• Is currently participating in or has participated in another clinical trial within the last 4 weeks and received other investigational drug treatments. If the participant is in the follow-up phase of a previous clinical trial and has had at least 4 weeks since the last investigational drug or removal of investigational devices, they may be eligible for this study.
• Has known psychiatric disorders, alcoholism, substance abuse, or drug abuse.
• Is pregnant or breastfeeding.
• Has any active autoimmune disease, history of autoimmune disease, or disease requiring systemic corticosteroids or immunosuppressive therapy (e.g., \>10 mg/day prednisone or equivalent). Hormone replacement therapy (e.g., thyroid hormone, insulin, or physiological corticosteroid replacement for adrenal or pituitary insufficiency) is allowed.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

MeSH Terms

Conditions

Breast Neoplasms

Interventions

camrelizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Erwei Song, M.D.. Ph.D.

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shicheng Su, M.D.. Ph.D.

CONTACT

+86 13632394954; DCvaccine@126.com

Erwei Song, M.D.. Ph.D.

CONTACT

+86 15989002838; DCvaccine@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Study Record Dates

• First Submitted: July 28, 2024
• First Posted: July 31, 2024
• Study Start: December 1, 2024
• Primary Completion: April 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: July 31, 2024

Record last verified: 2024-07