YS247 (Neoantigen-Pulsed DC Vaccine) for Metastatic Prostate Cancer

Official title

A Phase I, Single-Arm, Open-Label, Dose-Escalation Study to Evaluate the Safety and Preliminary Efficacy of Autologous Neoantigen-Pulsed Dendritic Cell Vaccine (YS247) in Patients With Metastatic Castration-Resistant Prostate Cancer

Overview

This phase I study tests a personalized cancer vaccine (Neo-DC) for men with advanced prostate cancer (metastatic castration-resistant prostate cancer, or mCRPC) that has continued to grow despite standard hormone therapies and other treatments. The vaccine is custom-made for each participant using their own immune cells (dendritic cells) mixed with specific tumor markers (neoantigens) unique to their cancer. These neoantigens are identified through genetic sequencing of the patient's tumor. The goal is to help the body's immune system recognize and attack the cancer cells specifically. The study will enroll approximately 9 to 18 men and will test three different dose levels to find the safest amount. Participants will receive the vaccine as an injection under the skin every two weeks for a total of 4 doses over an 8-week treatment period. The main purpose is to evaluate the safety of this vaccine, determine the maximum tolerated dose, and identify any serious side effects. Researchers will also look at whether the vaccine helps lower PSA levels (a blood marker for prostate cancer), slows cancer growth, and stimulates an immune response against the tumor. Participants will be monitored closely during treatment and followed for several months afterward to assess long-term safety and effects.

Detailed description

This is a phase I, single-center, open-label, dose-escalation study evaluating the safety, tolerability, and preliminary efficacy of an autologous neoantigen-pulsed dendritic cell vaccine (Neo-DC, also known as YS247) in patients with metastatic castration-resistant prostate cancer (mCRPC).

Study Design:

The study employs a traditional "3+3" dose-escalation methodology with three sequential dose cohorts: 5×10⁶, 1×10⁷, and 1.5×10⁷ cells per injection. A sentinel dosing approach will be used within each cohort, where the first participant is observed for 4 weeks before subsequent participants are enrolled at that dose level.

Intervention:

The investigational product is an autologous cellular immunotherapy manufactured from patient-derived peripheral blood mononuclear cells (PBMCs) obtained via leukapheresis. Dendritic cells are differentiated ex vivo, loaded with personalized neoantigens identified through next-generation sequencing (NGS) of tumor tissue (fresh biopsy or archival specimen), and matured using cytokine activation (GM-CSF, IL-4, TNF-α, IFN-γ, PGE2). The final product is administered as a subcutaneous injection (0.3 mL per site, 1-3 sites per dose) in the axillary or inguinal regions every 2 weeks for 4 doses (total 8-week treatment period).

Study Population:

Approximately 9-18 adult male participants (≥18 years) with histologically confirmed metastatic prostate adenocarcinoma will be enrolled. Eligibility requires documented disease progression following at least one novel endocrine therapy (e.g., abiraterone or enzalutamide), ECOG performance status 0-1, and adequate organ function (hematologic, hepatic, renal, cardiac). Participants must provide tumor tissue for neoantigen screening and HLA typing during the screening period (up to 90 days before first dose).

Endpoints:

Primary: Incidence of dose-limiting toxicities (DLTs) during the first 4 weeks (following 2 doses), frequency of grade ≥3 treatment-emergent adverse events (TEAEs per CTCAE v5.0), and determination of the maximum tolerated dose (MTD).

Secondary: PSA response rate (PSA50, defined as ≥50% decline from baseline), median progression-free survival (PFS) assessed by RECIST 1.1 and PCWG3 criteria, objective tumor response rate, and disease control rate.

Exploratory: Immunogenicity assessed by peripheral blood neoantigen-specific T-cell frequency (IFN-γ ELISPOT), changes in tumor-infiltrating lymphocyte density (IHC), and biomarker analysis of the tumor microenvironment.

Assessments:

Safety monitoring includes clinical laboratory tests (hematology, chemistry, PSA, testosterone), physical examinations, vital signs, and adverse event collection throughout the study. Efficacy evaluations include serial PSA measurements every 4 weeks and radiographic imaging (CT/MRI, bone scan, PSMA-PET/CT) at baseline, week 8, and every 6-8 weeks thereafter until progression. Immune response assessments will be conducted at baseline and week 8 (end of treatment).

Follow-up:

Participants will undergo safety follow-up at 60±7 days after the last dose. Long-term efficacy follow-up includes monthly visits for the first 6 months post-treatment, then every 2 months until disease progression, initiation of new anticancer therapy, loss to follow-up, or death. Survival status will be monitored via telephone follow-up monthly thereafter.

Statistical Considerations:

The sample size of 9-18 participants is based on the 3+3 dose-escalation design with 3 dose levels (3-6 participants per cohort). Safety and efficacy analyses will be performed on the safety analysis set and full analysis set, respectively, using descriptive statistics. Time-to-event endpoints (PFS, OS) will be estimated using Kaplan-Meier methods.

Interventions

• Biological Autologous Neoantigen-Pulsed Dendritic Cell Vaccine
  Personalized autologous dendritic cell vaccine manufactured from patient-derived peripheral blood mononuclear cells (PBMCs). Dendritic cells are differentiated ex vivo using GM-CSF and IL-4, loaded with patient-specific synthetic neoantigen peptides (identified via NGS sequencing of tumor tissue), and matured using TNF-α, IFN-γ, and PGE2. The vaccine is administered subcutaneously at 1-3 sites (axillary or inguinal lymph node regions) every 2 weeks for a total of 4 doses. Each injection site rec

Primary outcome measures

• Incidence of Dose-Limiting Toxicities (DLTs) [Time frame: From first dose through 60 days after the last dose (up to approximately 3 months)]
• Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs) [Time frame: From first dose through 60 days after the last dose (up to approximately 3 months)]
• Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) [Time frame: From first dose through 60 days after the last dose (up to approximately 3 months)]

Secondary outcome measures (8)

• Prostate-Specific Antigen (PSA) Response Rate (PSA50) [Time frame: From baseline through end of study (up to approximately 24 months)]
• Progression-Free Survival (PFS) [Time frame: From first dose until disease progression, death, or end of study (up to approximately 24 months)]
• Objective Response Rate (ORR) [Time frame: From baseline through end of study (up to approximately 24 months)]
• Disease Control Rate (DCR) [Time frame: From baseline through end of study (up to approximately 24 months)]
• Duration of Response (DOR) [Time frame: From date of first response to disease progression or death (up to approximately 24 months)]
• Neoantigen-Specific T-cell Immune Response [Time frame: Baseline and Week 8 (up to 2 months from first dose)]
• Tumor-Infiltrating Lymphocyte (TIL) Density [Time frame: Baseline and Week 8 (up to 2 months from first dose)]
• Overall Survival (OS) [Time frame: From first dose until death or end of study (up to approximately 36 months)]

Eligibility criteria

Inclusion criteria

• Male, age ≥18 years, with life expectancy ≥6 months.
• Histologically confirmed prostate adenocarcinoma with documented metastatic disease (bone, lymph nodes, or visceral organs) by recent whole-body MRI, bone scintigraphy (ECT), or PSMA-PET/CT.
• Confirmed metastatic castration-resistant prostate cancer (mCRPC) with documented disease progression after ≥1 line of novel endocrine therapy (e.g., abiraterone or enzalutamide).
• ECOG performance status 0-1.
• Availability of tumor tissue (fresh biopsy or archival specimen) for neoantigen screening.
• Willingness to undergo long-term follow-up.
• Provision of signed informed consent form by participant or legally authorized representative prior to study procedures.
• Willingness to undergo prostate biopsy if required for tissue acquisition. Adequate organ function as defined by laboratory values at screening: Absolute neutrophil count (ANC) >1.5×10⁹/L; Platelet count >100×10⁹/L; Hemoglobin >90 g/L; Total bilirubin, ALT, and AST within normal laboratory limits; Serum creatinine <133 μmol/L (or <1.5 mg/dL); INR <1.3 (or <3.0 if on warfarin or other anticoagulants); Albumin >30 g/L; Left ventricular ejection fraction (LVEF) ≥45% Negative for HIV, HBV (HBV DNA ≤500 IU/mL acceptable), and HCV (HCV RNA negative); No clinically significant ECG abnormalities.

Exclusion criteria

• History of other malignancies within the past 5 years (except non-melanoma skin cancer or carcinoma in situ with documented disease-free survival >5 years).
• Symptomatic central nervous system metastases.
• Uncontrolled active or persistent infection requiring systemic therapy.
• Systemic corticosteroid therapy within 4 weeks prior to enrollment (equivalent to >20 mg/day prednisone).
• Prior immunomodulatory therapy within 3 months, including but not limited to IL-2, CTLA-4 inhibitors, PD-1/PD-L1 inhibitors, CD40 agonists, or CD137 agonists (except adjuvant IFN-α for high-risk melanoma).
• Prior investigational prostate cancer-targeted vaccine therapy or cellular therapy within 3 months.
• Receipt of other investigational products within 2 months prior to enrollment.
• Known, confirmed, or suspected autoimmune disease or immunosuppressive condition.
• History of severe allergic reaction to any prior vaccination (for infectious disease prevention).
• Major cardiovascular events within 6 months prior to first dose, including acute coronary syndrome, aortic dissection, or stroke; or presence of severe cardiovascular disease requiring clinical intervention.
• Active autoimmune diseases (e.g., rheumatoid arthritis, systemic lupus erythematosus).
• Receipt of live vaccines within 4 weeks prior to first study treatment or planned during the study period.
• Uncontrolled hypertension (despite optimal medical management).
• Substance abuse or any psychological condition that, in the investigator's judgment, may interfere with study participation or results.
• Investigator's assessment of insufficient compliance or presence of other severe systemic diseases that would make the participant unsuitable for the study.
• High tumor burden as assessed by imaging, deemed unsuitable by the investigator.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Changhai Hospital — Shanghai

Identifiers

NCT: NCT07583160 · CHEC2026-049

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗