"neoBREASTIM": A Phase 2 Study of Atezolizumab Plus RP1 Oncolytic Immunotherapy in the NeoAdjuvant Setting of Triple-Negative Breast Cancer (TNBC)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- Safety of the combination Atezolizumab plus RP1 oncolytic during the safety run-in phase
研究概览
简要总结
Neoadjuvant treatment is an important part of the treatment strategy for locally advanced TNBC having established a positive and significant correlation of pathologic Complete Response (pCR) with long-term clinical benefit such as Event-Free Survival (EFS) and Overall Survival (OS) as shown via large meta-analysis. Much effort has been made to identify novel agents and new drug combinations that can improve pCR rates in this specific clinical setting, which is the leading rationale to evaluate RP1 oncolytic immunotherapy in combination with Atezolizumab.
详细描述
The combination of RP1 plus Atezolizumab, while being expected to result in increased efficacy, is not expected to result in significant additional toxicity, as compared to either agent alone. Capitalizing on the strong prognostic and predictive value of the TIL infiltrate in early-stage TNBC and the capacity of circulating tumor DeoxyriboNucleic Acid (ctDNA) detection to predict response to immunotherapy and NeoAdjuvant Chemotherapy (NAC), neoBREASTIM - a single-arm phase 2 study - will evaluate a novel, biomarker-driven combination of Atezolizumab plus RP1 oncolytic immunotherapy in the neo-adjuvant setting of patients diagnosed with early-stage, TIL-high TNBC.
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
- Female
- 接受健康志愿者
- 否
入选标准
- •Female subject
- •Age ≥ 18 years old.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤
- •Newly diagnosed Triple-Negative Breast Cancer (TNBC), defined as the absence of estrogen expression and progesterone expression, and of Human Epidermal growth factor Receptor 2 (HER2) overexpression, must be determined by local testing of a screening tumor sample as defined by American Society of Clinical Oncology/College of American Pathologists guidelines.
- •TNBC defined as the following combined primary tumor (T), regional lymph node (N), and metastatic (M) American Joint Committee on Cancer staging criteria: cT ≥15 - ≤30 mm, N0, M0 according to Mammogram, breast Ultrasound and MRI, and PET-CT. In case of a difference in the measurement of the primary tumor among different imaging methods, the breast MRI measurement is the reference.
- •Unicentric, unifocal and unilateral disease.
- •Tumor-infiltrating lymphocytes (TILs) ≥ 30%, as defined by the International TILs Working Group
- •ctDNA dosing at baseline.
- •Agreement to provide tissue samples (tumor biopsy at screening and on-treatment), and at surgery for immune monitoring and translational research activities.
- •Agreement to perform blood samples at screening, on-treatment, and at surgery for immune monitoring and translational research activities.
排除标准
- •Inflammatory breast cancer.
- •Prior treatment with an oncolytic virus-based therapy.
- •Patients with active significant herpetic infections or prior complications of Herpes Simplex Virus-1 (HSV-1) infection.
- •Patients who require intermittent or chronic use of systemic (oral or IV) antivirals with known antiherpetic activity (e.g., acyclovir).
- •Diagnosis of immunodeficiency.
- •Has active autoimmune disease (e.g. inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, and multiple sclerosis, celiac disease, Wegener's granulomatosis) that has required systemic treatment in the past 3 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
- •Prior systemic immunosuppressive medication (except physiologic corticosteroid replacement therapy) within 30 days of planned start of study therapy.
- •Any live (attenuated) vaccine within 14 days of planned start of study therapy.
- •Prior immunotherapy, including tumor vaccine, cytokine, anti-CTLA4, PD-1/PD-L1 blockade or similar agents, T cell receptor-based (TCR-based) or Chimeric Antigen Receptor-T (CAR-T) cell based adoptive cell therapy.
- •Known history of, or any evidence of active, non-infectious pneumonitis.
结局指标
主要结局
Safety of the combination Atezolizumab plus RP1 oncolytic during the safety run-in phase
时间窗: 9 months
Incidence of combination Atezolizumab plus RP1 adverse events (AEs) graded according to NCI CTCAE v5.0 and nature and severity
Toxicity of the combination Atezolizumab plus RP1 oncolytic immunotherapy during the safety run-in phase.
时间窗: 9 months
Dose Limiting Toxicity (DLT) during the first cycle of treatment of the combination Atezolizumab plus RP1 oncolytic immunotherapy
Residual Cancer Burden (RCB) 0-1 during the phase II part
时间窗: 30 months
Rate of RCB 0-1 at time of surgery (in patients with no increase in ctDNA after cycle 3)
次要结局
- Safety and toxicity of the combination Atezolizumab plus RP1 oncolytic immunotherapy(60 months)
- Correlation between RCB rates and response by Positron Emission Tomography-Scan (PET-CT) or breast MRI(60 months)
- Percentage of TILs(30 months)
- Breast Conservation Surgery (BCS)(30 months)
- Correlation between RCB rates and radiomics analyses(30 months)
- Invasive disease-free survival (iDFS)(60 months)
- Pre-treatment expression of Programmed Death-Ligand 1 (PD-L1)(30 months)
- Response rate of RCB Score <= 1 at three cycles(26 months)
- RCB rates and response(60 months)