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A Study of the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Participants With Locally Advanced and/or Metastatic Carcinoembryonic Antigen (CEA)-Positive Solid Tumors

2020年2月10日 更新者：Hoffmann-La Roche

An Open-Label, Multicenter, Dose Escalation and Expansion Phase Ib Study to Evaluate the Safety, Pharmacokinetics, and Therapeutic Activity of RO6958688 in Combination With Atezolizumab in Patients With Locally Advanced and/or Metastatic CEA-Positive Solid Tumors

This is an open-label, multicenter, dose-escalation and expansion Phase Ib clinical study of RO6958688 in combination with atezolizumab. Part I of the study is subdivided into parts IA and IB. Part IA is dose escalation with a starting dose of 5 mg of RO6958688 given QW (once a week) and a fixed, flat dose of 1200 mg given Q3W (every 3 weeks) of atezolizumab, to evaluate the safety and determine the MTD of RO6958688 in combination with atezolizumab. Part IB is a dose/schedule finding part that will explore different administration schedules of RO6958688 in combination with atezolizumab (1200 mg Q3W) to establish the appropriate dose/schedule of RO6958688 in combination with atezolizumab.

研究概览

地位

完全的

条件

干预/治疗

研究类型

介入性

注册 (实际的)

228

阶段

  • 阶段1

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习地点

  • 丹麦
      • København Ø、丹麦、2100
        • Rigshospitalet; Onkologisk Klinik
  • 加拿大
    • Ontario
      • Toronto、Ontario、加拿大、M5G 1Z5
        • Princess Margaret Cancer Center
  • 意大利
    • Campania
      • Napoli、Campania、意大利、80131
        • IRCCS IST. Tumori Fondaz. Pascale; S.C. Oncologia Medica,Melanoma,Immunoterapia E Terapie Innovative
    • Toscana
      • Siena、Toscana、意大利、53100
        • Azienda Ospedaliera Universitaria Senese, U.O.C. Immunoterapia Oncologica
  • 法国
      • Lyon、法国、69373
        • Centre Leon Berard; Departement Oncologie Medicale
      • Villejuif、法国、94805
        • Institut Gustave Roussy
  • 美国
    • California
      • Santa Monica、California、美国、90404
        • UCLA Cancer Center
      • Stanford、California、美国、94305
        • Stanford Comprehensive Cancer Center
    • Colorado
      • Aurora、Colorado、美国、80045
        • University of Colorado
    • Connecticut
      • New Haven、Connecticut、美国、06510
        • Smilow Cancer Hospital at Yale- New Haven Oncology Investigational Drug Pharmacy
    • Massachusetts
      • Boston、Massachusetts、美国、02215
        • Dana Farber Can Ins
    • New York
      • New York、New York、美国、10065
        • Memorial Sloan Kettering Cancer Center
      • New York、New York、美国、10032
        • Columbia Univ Med Ctr
    • North Carolina
      • Durham、North Carolina、美国、27710
        • Duke Cancer Center
    • South Carolina
      • Charleston、South Carolina、美国、29425
        • Medical University of South Carolina
    • Tennessee
      • Germantown、Tennessee、美国、38138
        • Sarah Cannon Cancer Center
    • Texas
      • Houston、Texas、美国、77030
        • MD Anderson Cancer Center
  • 荷兰
      • Amsterdam、荷兰、1066 CX
        • Antoni Van Leeuwenhoek Ziekenhuis; Gastro-Enterologie
  • 西班牙
      • Barcelona、西班牙、08003
        • Hospital del Mar; Servicio de Oncologia
      • Barcelona、西班牙、08035
        • Hospital Univ Vall d'Hebron; Servicio de Oncologia
      • Madrid、西班牙、28041
        • Hospital Universitario 12 de Octubre; Servicio de Oncologia
      • Madrid、西班牙、28040
        • Start Madrid-FJD, Hospital Fundacion Jimenez Diaz
      • Madrid、西班牙、28050
        • START Madrid. Centro Integral Oncologico Clara Campal; CIOCC
    • Navarra
      • Pamplona、Navarra、西班牙、31008
        • Clinica Universitaria de Navarra; Servicio de Oncologia

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

18年 及以上 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

Inclusion Criteria

  • Confirmed locally advanced and/or metastatic solid tumor, with at least one tumor lesion of accessible non-critical location to biopsy, in participants who have progressed on a standard therapy, are intolerant to standard therapy, and/or are non-amenable to standard therapy
  • Radiologically measurable and clinically evaluable disease (as per RECIST v1.1)
  • Life expectancy (in the opinion of the investigator) of at least 12 weeks and lactate dehydrogenase (LDH) levels </= 2.5 ULN (upper limit of normal)
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0-1
  • All acute toxic effects of any prior radiotherapy, chemotherapy, or surgical procedure must have resolved to Grade </= 1 or returned to baseline except alopecia (any grade) and Grade 2 peripheral neuropathy
  • Adequate hematological, liver, and renal function
  • Negative serum pregnancy test within 7 days prior to study treatment in premenopausal women and women </= 2 years after start of menopause (menopause is defined as amenorrhea for more than 2 years)
  • Participants must agree to remain abstinent or be willing to use effective methods of contraception as defined in the protocol
  • Participants with non-colorectal cancer should have confirmed CEA expression in tumor tissue. For colorectal cancer (CRC), the CEA assessment should be performed but the result is not required for participant selection

Exclusion Criteria

  • Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
  • Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for at least 2 weeks prior to enrollment
  • Leptomeningeal disease
  • Participants with paraspinal, paratracheal, and mediastinal pathological lesions larger than 2 cm unless they are previously irradiated
  • Malignancies within 5 years prior to enrollment, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
  • Significant, uncontrolled concomitant diseases which could affect compliance with the protocol or interpretation of results
  • Uncontrolled hypertension, unstable angina, congestive heart failure (CHF), serious cardiac arrhythmia requiring treatment history of myocardial infarction within 6 months of enrollment
  • Administration of a live, attenuated vaccine within 28 days before Cycle 1 Day 1 or anticipation that such a live attenuated vaccine will be required during the study
  • Human Inmmunodeficiency Virus (HIV), active Hepatitis B or Hepatitis C (HCV)
  • Severe infections within 28 days prior to Cycle 1 Day 1, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia or active tuberculosis
  • Received oral or intravenous (IV) antibiotics within 14 days prior to Day 1
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug
  • Major surgery or significant traumatic injury less than 28 days prior to Cycle 1 Day 1 (excluding biopsies) or anticipation of the need for major surgery during study treatment
  • Known history of autoimmune disease as defined in the protocol
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis (including drug induced) on screening chest CT scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Participants with bilateral lung lesions and dyspnea and/or oxygen saturation level (SaO2) less than 92% (at rest, room air and exertion) or participants with lobectomy or pneumonectomy with lung metastases in the remaining lung and either dyspnea or SaO2 less than 92% (at rest, room air and exertion) at baseline
  • Pregnant or breast-feeding
  • Known hypersensitivity to any of the components of RO6958688 and atezolizumab; hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • Investigational therapy (defined as treatment for which there is no regulatory authority approved indication) or last dose of prior immunotherapies within 28 days prior to Cycle 1 Day 1. Participants previously treated with anti-programmed death-ligand 1 (PD-L1), or anti-PD-1 are excluded
  • Last dose of any approved anti-cancer therapy within 28 days prior to the first RO6958688 infusion
  • Prior systemic corticosteroids greater than 10mg prednisone (or equivalent) within 14 days of Cycle 1 Day 1. Inhaled and/or topical steroids are permitted
  • Expected need for regular immunosuppressive therapy
  • Radiotherapy within the last 28 days before Cycle 1 Day 1 with the exception of limited-field palliative radiotherapy

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：顺序分配
  • 屏蔽：无（打开标签）

武器和干预

参与者组/臂
干预/治疗
实验性的：Dose-Escalation (Part IA): RO6958688 + Atezolizumab
Participants will receive RO6958688 weekly (QW) at escalating doses starting at 5 mg, in combination with a fixed dose (1200 mg) of atezolizumab every 3 weeks (Q3W). RO6958688 dosage will not exceed the MTD if defined in the BP29541 study.
药品：Atezolizumab
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion.
其他名称：
  • 技术中心
药品：RO6958688

RO6958688 is administered by IV infusion

In Part IA: RO6958688 is administered weekly (QW) on days 1,8 and 15 of each 21-day cycle.

In Part 1b: RO6958688 is administered weekly (QW) or every 3 weeks (Q3W). Cohort A: RO6958688 starting dose will be 100 mg either QW or Q3W.

Step Up dose cohorts: RO6958688 starting dose will be 40mg and increase with each administration up to the MTD or 1200 mg whichever is lower.
实验性的：Dose/Schedule Finding (Part IB): RO6958688 + Atezolizumab

Part IB will explore different RO6958688 administration schedules in combination with atezolizumab, consisting of:

Cohort A: will compare the QW vs Q3W dosing schedules at a flat dose of RO6958688.

Step Up dosing schedules: RO6958688 dose will start at 40 mg and increase with each administration up to the MTD or 1200 mg, whichever occurs first.
药品：Atezolizumab
Atezolizumab will be administered at a fixed dose of 1200 milligrams (mg) by intravenous (IV) infusion.
其他名称：
  • 技术中心
药品：RO6958688

RO6958688 is administered by IV infusion

In Part IA: RO6958688 is administered weekly (QW) on days 1,8 and 15 of each 21-day cycle.

In Part 1b: RO6958688 is administered weekly (QW) or every 3 weeks (Q3W). Cohort A: RO6958688 starting dose will be 100 mg either QW or Q3W.

Step Up dose cohorts: RO6958688 starting dose will be 40mg and increase with each administration up to the MTD or 1200 mg whichever is lower.

研究衡量的是什么？

主要结果指标

结果测量
大体时间
具有剂量限制毒性 (DLT) 的参与者百分比
大体时间：第 1 天到第 21 天
第 1 天到第 21 天
Number of Participants with Adverse Events (AEs)
大体时间：Baseline up to 60 months
Baseline up to 60 months
Maximum-Tolerated Dose (MTD) of RO6958688
大体时间：Part IA: Day 1 up to Day 21; Part IB Step-up Cohorts: Day 1 up to Day 7 after each dose escalation
Part IA: Day 1 up to Day 21; Part IB Step-up Cohorts: Day 1 up to Day 7 after each dose escalation
Recommended Phase II Dose (RP2D) of RO6958688
大体时间：Day 1 up to 60 months
Day 1 up to 60 months

次要结果测量

结果测量
措施说明
大体时间
Pharmacokinetic (PK): Area Under the Concentration-Time Curve (AUC) of RO6958688
大体时间：Baseline up to 60 months
Baseline up to 60 months
PK: Volume of Distribution at Steady State (Vss) of RO6958688
大体时间：Baseline up to 60 months
Baseline up to 60 months
PK: Maximum Serum Concentration (Cmax) of RO6958688
大体时间：Baseline up to 60 months
Baseline up to 60 months
PK: Clearance (CL) of RO6958688
大体时间：Baseline up to 60 months
Baseline up to 60 months
PK: AUC of Atezolizumab
大体时间：Baseline up to 60 months
Baseline up to 60 months
PK: Vss of Atezolizumab
大体时间：Baseline up to 60 months
Baseline up to 60 months
PK: Cmax of Atezolizumab
大体时间：Baseline up to 60 months
Baseline up to 60 months
PK: CL of Atezolizumab
大体时间：Baseline up to 60 months
Baseline up to 60 months
Pharmacodynamics: Immune Cell Numbers as Assessed using Flow Cytometry
大体时间：Pre-infusion (1 hour before infusion start) on Day 1 of Cycles 1, 2, 3, 6; Cycle 1 Days 2 and 8 (cycle length=21 days)
Pre-infusion (1 hour before infusion start) on Day 1 of Cycles 1, 2, 3, 6; Cycle 1 Days 2 and 8 (cycle length=21 days)
Percentage of Participants with Objective Response (Partial Response [PR] or Complete Response [CR] as Assessed Using Response Evaluation Criteria in Solid Tumors [RECIST])
大体时间：Baseline up to 60 months
Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
Baseline up to 60 months
Percentage of Participants with Disease Control (PR, CR, or Stable Disease [SD]) as Assessed Using RECIST
大体时间：Baseline up to 60 months
Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
Baseline up to 60 months
Percentage of Participants with Stable Disease (SD) as Assessed Using RECIST
大体时间：Baseline up to 60 months
Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
Baseline up to 60 months
Duration of Response (DOR) as Assessed Using RECIST
大体时间：From initial objective response (PR or CR to the first disease progression or death from any cause (up to 60 months)
Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
From initial objective response (PR or CR to the first disease progression or death from any cause (up to 60 months)
Progression-Free Survival (PFS) according to RECIST V1.1
大体时间：From first study treatment to the first occurrence of objective disease progression or death from any cause (up to 60 months)
Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
From first study treatment to the first occurrence of objective disease progression or death from any cause (up to 60 months)
Overall Survival (OS)
大体时间：From first study treatment to death from any cause (up to 60 months)
Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
From first study treatment to death from any cause (up to 60 months)
Best Overall Response (BOR)
大体时间：Baseline up to 60 months
Assessed at screening and after the start of treatment every 8 weeks for the first year, then every 12 weeks thereafter until disease progression or treatment discontinuation.
Baseline up to 60 months

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Hoffmann-La Roche

出版物和有用的链接

负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。

一般刊物

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (实际的)

2016年1月7日

初级完成 (实际的)

2020年1月13日

研究完成 (实际的)

2020年1月13日

研究注册日期

首次提交

2016年1月6日

首先提交符合 QC 标准的

2016年1月6日

首次发布 (估计)

2016年1月8日

研究记录更新

最后更新发布 (实际的)

2020年2月12日

上次提交的符合 QC 标准的更新

2020年2月10日

最后验证

2020年2月1日

更多信息

与本研究相关的术语

其他相关的 MeSH 术语

其他研究编号

  • WP29945
  • RG7802 (其他标识符：Roche)
  • 2015-003771-30 (EudraCT编号)

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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