A Phase 1 / 2 Multiple-indication Biomarker, Safety, and Efficacy Study in Advanced or Metastatic Gastrointestinal Cancers Exploring Treatment Combinations With Pelareorep and Atezolizumab
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 122
- 试验地点
- 30
- 主要终点
- Overall Response Rate (ORR) for Cohort 1, 2, 4, and 5
研究概览
简要总结
This is an open-label, phase 1/2, multiple-indication platform study to explore safety, potential predictive immune-related biomarkers, and early efficacy (as measured by objective response rate [ORR; Cohorts 1,2, 4,and 5] and disease control rate [DCR; Cohort 3]) in patients with advanced or metastatic gastrointestinal (GI) tumors. Cohorts 1-4 are not randomized; however, Cohort 5 is comprised of two treatment arms to which patients are randomized in a 1:1 ratio.
详细描述
The overall aim is to assess safety, predictive biomarkers, and preliminary efficacy as assessed by tumor response criteria at week 16 for cohorts1, 2, 3, and 4, and best overall response rate and OS in Cohort 5. If a cohort shows a promising ORR in Stage 1 of the Simon two-stage design, that cohort may be expanded to enroll additional patients (up to 50 patients in Cohorts 1 and 3 , up to 28 patients in Cohort 4, and up to 64 patients in Cohort 5) in an extension phase per predetermined statistical conditions. In addition, either or both arms of Cohort 5 may expand if the data collected in Stage 1 suggest that expansion may help in assessing the potential survival benefit of the investigational therapy(ies). In this study, we hypothesize that treatment with pelareorep will prime the tumor microenvironment (TME) for checkpoint blockade therapy, thereby increasing PD-L1 expression and the number of new T cell clones within the tumor, both of which are associated with increased response to checkpoint blockade.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Cohorts 1-5 Inclusion Criteria:
- •ECOG performance status of 0 or 1
- •Have measurable lesions per RECIST v1.1
- •Patients must have adequate hematological, renal, and hepatic function
- •Have recovered to ≤grade 1 or baseline for all adverse events (AEs) due to previous therapies or surgeries.
- •For female patients of childbearing potential and male patients with partners of childbearing potential, agreement to use a highly-effective form(s) of contraception and to continue its use for 6 months after the last dose of study drug.
排除标准
- •Undergone systemic chemotherapy, radiotherapy, or surgery, <4 weeks before study treatment.
- •Received previous treatment with immune checkpoint inhibitors
- •Uncontrolled or severe cardiac disease
- •Active, uncontrolled infections
- •Symptomatic brain metastasis
- •Interstitial lung disease with symptoms or signs of activity.
- •Autoimmune disease that has required systemic treatment in the past 2 years with disease modifying agents, corticosteroids, or immunosuppressive drugs.
- •A seizure disorder that requires pharmacotherapy.
- •Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation.
- •A non-healing wound, non-healing ulcer, or non-healing bone fracture within 4 weeks prior to the start of study drug.
- •Women who are pregnant or breastfeeding.
- •A diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy
- •Any vaccine within 28 days prior to first treatment or during the first cycle of study treatment.
- •Exclusion Criteria:
- •In Cohort 1, 2, 3, 4: Life expectancy less than 3 months
- •In Cohort 1, 2, 3: known active Hepatitis B (HBV) or Hepatitis C (HCV) infection that requires anti-viral treatment.
- •In Cohort 4: Prior HIV infection if the CD4+ T cell is <300 cells/µl
- •In Cohort 5: Known low or absent dihydropyrimidine dehydrogenase (DPD) activity.
- •In Cohort 5: Known leptomeningeal disease.
- •In Cohort 5: History of another primary cancer within the last 3 years with the exception of non-melanoma skin cancer, early-stage prostate cancer, or curatively treated cervical carcinoma in-situ
研究组 & 干预措施
Cohort 5: Metastatic PDAC 1L
Patients with 1L metastatic PDAC: Pelareorep and modified FOLFIRINOX (mFOLFIRINOX) with or without atezolizumab
干预措施: mFOLFIRINOX Treatment Regimen (Drug)
Cohort 1: Metastatic Pancreatic Cancer 1L
Patients with first-line (1L) locally advanced/metastatic unresectable pancreatic ductal adenocarcinoma (PDAC): Pelareorep and atezolizumab added to gemcitabine and nab-paclitaxel
干预措施: Atezolizumab (Drug)
Cohort 2: Metastatic Colorectal Cancer 1L (MSI-H/dMMR)
Patients with 1L metastatic colorectal cancer (mCRC), limited to microsatellite instability-high (MSIH) or mismatch repair deficient (dMMR) tumors: Pelareorep and atezolizumab
干预措施: Atezolizumab (Drug)
Cohort 1: Metastatic Pancreatic Cancer 1L
Patients with first-line (1L) locally advanced/metastatic unresectable pancreatic ductal adenocarcinoma (PDAC): Pelareorep and atezolizumab added to gemcitabine and nab-paclitaxel
干预措施: Pelareorep (Drug)
Cohort 1: Metastatic Pancreatic Cancer 1L
Patients with first-line (1L) locally advanced/metastatic unresectable pancreatic ductal adenocarcinoma (PDAC): Pelareorep and atezolizumab added to gemcitabine and nab-paclitaxel
干预措施: Gemcitabine and nab-paclitaxel (Drug)
Cohort 3: Metastatic Colorectal Cancer 3L
Patients with third-line (3L) mCRC independent of microsatellite instability (MSI)/dMMR status: Pelareorep and atezolizumab added to trifluridine/tipiracil
干预措施: Trifluridine Tipiracil (Drug)
Cohort 2: Metastatic Colorectal Cancer 1L (MSI-H/dMMR)
Patients with 1L metastatic colorectal cancer (mCRC), limited to microsatellite instability-high (MSIH) or mismatch repair deficient (dMMR) tumors: Pelareorep and atezolizumab
干预措施: Pelareorep (Drug)
Cohort 3: Metastatic Colorectal Cancer 3L
Patients with third-line (3L) mCRC independent of microsatellite instability (MSI)/dMMR status: Pelareorep and atezolizumab added to trifluridine/tipiracil
干预措施: Pelareorep (Drug)
Cohort 3: Metastatic Colorectal Cancer 3L
Patients with third-line (3L) mCRC independent of microsatellite instability (MSI)/dMMR status: Pelareorep and atezolizumab added to trifluridine/tipiracil
干预措施: Atezolizumab (Drug)
Cohort 4: Metastatic Unresectable Anal Cancer >/=2L
Patients with >/= 2L locally advanced/metastatic unresectable squamous cell carcinoma of the anal canal (SCCA) of viral or non-viral origin after prior systemic chemotherapy: Pelareorep and atezolizumab
干预措施: Pelareorep (Drug)
Cohort 4: Metastatic Unresectable Anal Cancer >/=2L
Patients with >/= 2L locally advanced/metastatic unresectable squamous cell carcinoma of the anal canal (SCCA) of viral or non-viral origin after prior systemic chemotherapy: Pelareorep and atezolizumab
干预措施: Atezolizumab (Drug)
Cohort 5: Metastatic PDAC 1L
Patients with 1L metastatic PDAC: Pelareorep and modified FOLFIRINOX (mFOLFIRINOX) with or without atezolizumab
干预措施: Pelareorep (Drug)
Cohort 5: Metastatic PDAC 1L
Patients with 1L metastatic PDAC: Pelareorep and modified FOLFIRINOX (mFOLFIRINOX) with or without atezolizumab
干预措施: Atezolizumab (Drug)
结局指标
主要结局
Overall Response Rate (ORR) for Cohort 1, 2, 4, and 5
时间窗: At week 16 (within each cohort)
Proportion of patients with complete response \[CR\], partial response \[PR\] assessed by the investigators and/or central reader according to RECIST v1.1
Disease Control Rate (DCR) - Cohort 3
时间窗: at week 16
DCR (complete response \[CR\], partial response \[PR\], and stable disease \[SD\]) assessed by the investigators according to RECIST v 1.1.
Overall Survival (OS) - Cohort 5
时间窗: Cohort 5: From the date of randomization through long term follow up at 2 years
OS is defined as the time from date of first treatment to death from any cause
次要结局
- Progression Free Survival (PFS)(From initiation of treatment to objective progression or death from any cause, whichever occurs first, up to two years)
- Duration of Response (DOR)(From initiation of treatment to disease progression or death from any cause, whichever occurs first, up to two years)
- Disease Control Rate (DCR)(From initiation of treatment to disease progression or death from any cause, whichever occurs first, up to two years)
- Overall Response Rate (ORR) - Cohort 1-4(From initiation of treatment to disease progression or death from any cause, whichever occurs first, up to two years)
- Overall Survival (OS) - Cohort 1-4(From the date of randomization through long term follow up at 3 years)