A Pilot Study Comparing Neoadjuvant and Adjuvant GVAX vs a Mutated KRAS Peptide Vaccine Given With Anti-PD-1 and Anti-CD137 for the Treatment of Surgically Resectable Pancreatic Adenocarcinoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 38
- 试验地点
- 1
- 主要终点
- Dose Limiting Toxicities in Phase I participants
研究概览
简要总结
The purpose of this study is to determine the optimal dose of AGEN2373 that is safe when given in combination with balstilimab and Pancreatic GVAX Whole Cell Vaccine and evaluate the safety and clinical activity of balstilimab and AGEN2373 in combination with GVAX (Arm 1) or mKRASvax (Arm 2) in surgically resectable pancreatic adenocarcinoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have a newly diagnosed, biopsy-proven adenocarcinoma of the pancreas.
- •Tumor must be deemed resectable by the study team
- •Patient's acceptance to have a tumor biopsy.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0 -
- •Patients must have adequate organ and marrow function defined by study-specified laboratory tests and procedures.
- •Women of childbearing potential (WOCBP) must have a negative serum pregnancy test.
- •For both Women and Men, must use acceptable form of birth control while on study.
排除标准
- •Received any anti-pancreatic cancer therapy (symptomatic therapies are allowed), or any prior anti-cancer immunotherapy.
- •Diagnosed with another cancer whose natural history or treatment could interfere with safety or efficacy assessments on this study.
- •Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina, cardiac arrhythmia, metastatic cancer, or psychiatric illness/social situations that would limit compliance with study requirements.
- •Active autoimmune disease.
- •Systemic steroid therapy (> 10mg daily prednisone equivalent) or immunosuppressive therapy within 14 days of first dose of study drug administration.
- •Active infection requiring systemic therapy.
- •Known history of human immunodeficiency virus (HIV).
- •Active or chronic hepatitis B or hepatitis C.
- •Known active tuberculosis.
- •History of interstitial lung disease, non-infectious pneumonitis or uncontrolled lung diseases including pulmonary fibrosis, acute lung diseases, chronic obstructive pulmonary disease (COPD), asthma requiring medication, etc.
- •Prior allogeneic stem cell transplantation or organ transplantation.
- •Any major surgical procedure requiring general anesthesia ≤ 28 days before first dose of study drug.
- •Received a live vaccine ≤ 28 days before first dose of study drug.
- •History of severe hypersensitivity reaction to any monoclonal antibody
- •Concurrent participation in another therapeutic clinical study
- •Pregnant or breastfeeding
研究组 & 干预措施
Arm 1 - AGEN2373/Balstilimab/Cyclophosphamide/GVAX
干预措施: AGEN2373 (Drug)
Arm 1 - AGEN2373/Balstilimab/Cyclophosphamide/GVAX
干预措施: Balstilimab (Drug)
Arm 1 - AGEN2373/Balstilimab/Cyclophosphamide/GVAX
干预措施: Cyclophosphamide (Drug)
Arm 1 - AGEN2373/Balstilimab/Cyclophosphamide/GVAX
干预措施: GVAX (Drug)
Arm 2 - AGEN2373/Balstilimab/mKRASvax (1.8mg total peptides +0.5mg each poly-ICLC)
干预措施: AGEN2373 (RP2D) (Drug)
Arm 2 - AGEN2373/Balstilimab/mKRASvax (1.8mg total peptides +0.5mg each poly-ICLC)
干预措施: Balstilimab (Drug)
Arm 2 - AGEN2373/Balstilimab/mKRASvax (1.8mg total peptides +0.5mg each poly-ICLC)
干预措施: mKRASvax (Drug)
结局指标
主要结局
Dose Limiting Toxicities in Phase I participants
时间窗: 1 month
Phase I participants will be evaluated for dose limiting toxicities (DLTs) during the first 14 day cycle and 14 days post-operatively for the purpose of determining the recommended phase II dose of AGEN2373 when given concurrently with balstilimab and cancer vaccination.
Number of participants experiencing Grade 3 or Higher study drug-related toxicities
时间窗: 2 years
Number of participants experiencing study drug-related adverse events Grade 3 or higher as defined by CTCAE v5.0
Number of participants who form Intratumoral tertiary lymphoid structures (TLS)
时间窗: 2 weeks
Number of participants who form at least one tertiary lymphoid structure (TLS) following one cycle of study drugs. The presence of at least 50 CD20+ B cells and 50 CD3+ T cells in a ≥50 µM area of surgical tissue is considered "positive" for TLS.
次要结局
- Pathologic overall response rate (pORR)(evaluated at time of surgery, approximately 2 weeks from first dose of study drug)
- CD3+CD8+CD137+ T cell density in Tumor Tissue(evaluated at time of surgery, approximately 2 weeks from first dose of study drug)
- Change in peripheral interferon-gamma (IFNγ) producing mutant KRAS-specific T cells(13 weeks)