A Phase I, First-in-Human Study of Intratumoral Administration of CF33-hNIS-antiPDL1, A Novel Chimeric Oncolytic Poxvirus Encoding Human Sodium Iodide Symporter (HNIS) in Patients With Metastatic Triple Negative Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 9
- 试验地点
- 2
- 主要终点
- Incidence of adverse events
研究概览
简要总结
This phase I trial tests the safety, side effects, and best dose of CF33-hNIS-antiPDL1 in treating patients with triple negative breast cancer that has spread to other places in the body (metastatic). CF33-hNIS-antiPDL1 is an oncolytic virus. This is a virus that is designed to infect tumor cells and break them down.
详细描述
PRIMARY OBJECTIVE:
I. To determine the safety and tolerability of a novel chimeric oncolytic orthopoxvirus, oncolytic virus CF33-expressing hNIS/Anti-PD-L1 antibody (CF33-hNIS-antiPDL1), by the evaluation of toxicities including: type, frequency, severity, attribution, time course, reversibility and duration according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0 criteria.
SECONDARY OBJECTIVES:
I. To determine the optimal biologic dose (OBD) (defined as a safe dose that induces an immune response in tumors [increase checkpoint target PD-L1 by at least 5% and/or increase T cell infiltration by at least 10%]) and the recommended phase II dose (RP2D) for future expansion trial.
II. To determine tumor response rates by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 (primary) and immune-modified (i)RECIST (secondary).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Documented informed consent of the participant and/or legally authorized representative
- •Assent, when appropriate, will be obtained per institutional guidelines
- •Agreement to research biopsies on study, once during study and end of study, exceptions may be granted with study principal investigator (PI) approval
- •>= 18 years
- •Eastern Cooperative Oncology Group (ECOG) =< 2
- •Histologically confirmed metastatic triple negative breast cancer. Triple negative status will be defined as estrogen receptor (ER) and progesterone receptor (PR) =< 10% by immunohistochemistry (IHC) and HER2 negative, per American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines
- •Measurable disease by RECIST 1.1
- •Patients must have progressed on or been intolerant of at least 2 prior lines of therapy for advanced/metastatic disease. Patients that qualify for immunotherapy and/or PARP inhibitors must have progressed on or been intolerant of these agents
- •Fully recovered from the acute toxic effects (except alopecia) to =< grade 2 to prior anti-cancer therapy
- •Must have a superficial tumor (cutaneous, subcutaneous), breast lesion or nodal metastases amenable to safe repeated intratumoral injections per treating physician and interventional radiologist review
- •Absolute neutrophil count (ANC) >= 1,500/mm^3
- •NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement
- •Platelets >= 100,000/mm^3
- •NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
- •Total bilirubin =< 1.5 X upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) =< 2.5 x ULN
- •If liver metastases are present: AST =< 5 x ULN
- •Alanine aminotransferase (ALT) =< 2.5 x ULN
- •If liver metastases are present: ALT =< 5 x ULN
- •Serum creatinine =< 1.5 mg/dL or creatinine clearance of >= 50 mL/min per 24 hour urine test or the Cockcroft-Gault formula
- •Prothrombin (PT) =< 1.5 x ULN
- •Activated partial thromboplastin time (aPTT) =< 1.5 x ULN
- •Women of childbearing potential (WOCBP): negative serum pregnancy test
- •Agreement by females and males of childbearing potential* and their partners to use an effective method of birth control (defined as a hormonal or barrier method) or abstain from heterosexual activity for the course of the study through at least 6 months after the last dose of protocol therapy
- •Childbearing potential defined as not being surgically sterilized (men and women) or have not been free from menses for > 1 year (women only)
排除标准
- •Chemotherapy, biological therapy, immunotherapy or investigational therapy within 14 days prior to day 1 of protocol therapy
- •Major surgery or radiation therapy within 28 days of study therapy
- •Has received a vaccination within 30 days of first study injection
- •History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent
- •Clinically significant uncontrolled illness
- •Active infection requiring antibiotics
- •Known history of immunodeficiency virus (HIV)
- •Patients with a known history of hepatitis B or hepatitis C infection who have active disease as evidenced by hepatitis (Hep) B surface antigen status or Hep C polymerase chain reaction (PCR) status obtained within 14 days of cycle 1, day 1
- •Another malignancy within 3 years, except non-melanomatous skin cancer
- •Females only: Pregnant or breastfeeding
- •Patients may not have clinically unstable brain metastases. Patients may be enrolled with a history of treated brain metastases that are clinically stable for >= 4 weeks prior to start of study treatment
- •Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns with clinical study procedures
- •Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)
研究组 & 干预措施
Treatment (CF33-hNIS-antiPDL1)
Patients receive CF33-hNIS-antiPDL1 IT on days 1 and 15. Treatment repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity.
干预措施: Oncolytic Virus CF33-expressing hNIS/Anti-PD-L1 Antibody (Biological)
结局指标
主要结局
Incidence of adverse events
时间窗: Up to 30 days
Toxicity will be graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0. Observed toxicities/adverse events will be summarized in terms of type (organ affected or laboratory determination), severity, time of onset, duration, probable association with the study treatment and reversibility or outcome.
次要结局
- Progression free survival(Up to 1 year)
- Clinical benefit rate(Up to 6 months)
- Response rate based on immune related iRECIST(Up to 6 months)
- Optimal biologic dose(Up to 3 months)
- Response rate based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1(Up to 6 months)
- Overall survival(Up to 3 years)
- Immune Biomarker Expression(Up to 6 months)
- Event-free survival(Up to 3 years)
- Duration of response(Up to 3 years)