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在晚期肿瘤中评估 CCS1477 的研究

2026年9月1日 更新者：CellCentric Ltd.

一项开放标签 I/IIa 期研究，以评估 CCS1477 作为单一疗法和联合疗法在晚期实体瘤/转移性肿瘤患者中的安全性和有效性。

A Phase 1/2a study to assess the safety, tolerability, PK and biological activity of CCS1477 in patients with metastatic castration resistant prostate cancer, metastatic breast cancer, non-small cell lung cancer or advanced solid tumours.

研究概览

地位

完全的

条件

干预/治疗

详细说明

The Steering Committee closed selected cohorts, in accordance with its responsibilities, after findings from earlier cohorts indicated that further evaluation of those cohorts was no longer warranted. The remaining cohorts were completed as specified in the protocol. Therefore, the study was considered completed.

研究类型

介入性

注册 (实际的)

219

阶段

  • 阶段2
  • 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

  • 法国
      • Bordeaux、法国、33000
        • Institute Bergonie
      • Paris、法国、75015
        • Hôpital Europeen Georges Pompidou
      • Villejuif、法国、94805
        • Institute Gustave Roussy
  • 瑞典
      • Stockholm、瑞典、171 76
        • Karolinska Institute
  • 美国
    • Massachusetts
      • Boston、Massachusetts、美国、02215
        • Dana-Farber Cancer Institute
    • Pennsylvania
      • Philadelphia、Pennsylvania、美国、19107
        • Thomas Jefferson University, Sidney Kimmel Cancer Center
  • 英国
      • Belfast、英国、BT9 7AB
        • Belfast City Hospital
      • Birmingham、英国、B15 2TH
        • Queen Elizabeth Hospital Cancer Centre
      • Cambridge、英国、CB2 0QQ
        • Cambridge University Hospital
      • Edinburgh、英国、EH4 2XU
        • Edinburgh Cancer Centre Western General Hospital
      • Glasgow、英国、G12 0YN
        • The Beatson West of Scotland Cancer Centre
      • Leicester、英国、LE1 5WW
        • Leicester Royal Infirmary
      • Manchester、英国、M20 4BX
        • The Christie Hospital
      • Newcastle、英国、NE7 7DN
        • Freeman Hospital
      • Southampton、英国、SO16 6YD
        • University Hospital Southampton
      • Sutton、英国、SM2 5NG
        • Royal Marsden Hospital
  • 荷兰
      • Amsterdam、荷兰、1066 CX
        • Netherlands Cancer Institute (NKI)
  • 西班牙
      • Barcelona、西班牙、08035
        • Hospital Vall d'Hebron, VHIO
      • Madrid、西班牙、28050
        • START CIOCC Hospital Universitario HM

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:

  • Provision of consent
  • ECOG performance status 0-1
  • Assessable disease (by CT, MRI, bone scan or X-ray)
  • Adequate organ function
  • Highly effective contraception measures for duration of study

Additional inclusion criteria for mCRPC patients only:

  • Previously received abiraterone and/or enzalutamide (or equivalent anti-androgen), and docetaxel (unless ineligible or refused)

  • Progressive disease documented by one or more of the following:

    • Biochemical progression defined as at least 2 stepwise increases in a series of any 3 PSA values
    • Progression as defined by RECIST v1.1 guideline for assessment of malignant soft tissue disease.
    • Progression defined as two or more new metastatic bone lesions confirmed on bone scan from a previous assessment

  • PSA at screening ≥2 μg/L

  • Serum testosterone concentration ≤50 ng/dL

  • Serum albumin >2.5 g/dL

Additional inclusion criteria for patients in CCS1477 plus abiraterone combination arm:

  • Patients must have previously progressed on abiraterone treatment
  • Patients whose last dose of abiraterone is greater than 6 months prior to start of study treatment will receive a 4-week run-in treatment with abiraterone to confirm refractoriness to abiraterone treatment

Additional inclusion criteria for patients in CCS1477 plus enzalutamide combination arm:

  • Patients must have previously progressed on enzalutamide treatment
  • Patients whose last dose of enzalutamide is greater than 6 months prior to start of study treatment will receive a 4-week run-in treatment with enzalutamide to confirm refractoriness to enzalutamide treatment

Additional inclusion criteria for patients in mutation arm:

  • Advanced solid tumour with identification of markers which may indicate potential for response to p300/CBP inhibition. Markers include loss of function mutations in CREBBP, EP300 or ARID1A, MYC gene amplifications or rearrangements and androgen receptor (AR) gene amplifications or over-expression.

Exclusion Criteria:

  • Intervention with any chemotherapy, investigational agents or other anti-cancer drugs within 14 days or 5 half-lives of the first dose
  • Radiotherapy with a wide field of radiation or to more than 30% of the bone marrow within 4 weeks of the first dose of study treatment
  • Major surgical procedure or significant traumatic injury within 4 weeks of the first dose of study treatment
  • Strong inhibitors of CYP3A4 or CYP3A4 substrates with a narrow therapeutic range taken within 2 weeks of the first dose of study treatment
  • Strong inducers of CYP3A4 within 4 weeks of the first dose of study treatment
  • Statins; patients should discontinue statins prior to starting study treatment
  • Any unresolved reversible toxicities from prior therapy >CTCAE grade 1 at the time of starting study treatment
  • Any evidence of severe or uncontrolled systemic diseases
  • Any known uncontrolled inter-current illness
  • QTcF prolongation (> 480 msec).
  • Primary brain tumours or known or suspected brain metastases.

Additional exclusion criteria for patients in CCS1477 plus abiraterone combination arm:

  • Clinically significant cardiac abnormalities

Additional exclusion criteria for patients in CCS1477 plus enzalutamide combination arm:

  • History of seizures or other predisposing factors
  • Use of substrates with a narrow therapeutic index metabolised by CYP2C9 or CYP2C19 within 2 weeks of the first dose of study treatment
  • Clinically significant cardiac abnormalities

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：非随机化
  • 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：CCS1477 dose escalation - mCRPC

CCS1477 monotherapy in patients with mCRPC
药品：CCS1477

Capsules, oral
实验性的：CCS1477 expansion phase - mCRPC

CCS1477 monotherapy in patients with mCRPC
药品：CCS1477

Capsules, oral
实验性的：CCS1477 and abiraterone acetate, combination dose finding and expansion - mCRPC

CCS1477 plus abiraterone acetate in patients with mCRPC
药品：CCS1477

Capsules, oral

药品：Abiraterone acetate

Abiraterone acetate 500mg tablets plus prednisone/prednisolone
实验性的：CCS1477 and enzalutamide, combination dose finding and expansion - mCRPC

CCS1477 plus enzalutamide in patients with mCRPC
药品：CCS1477

Capsules, oral

药品：Enzalutamide

Enzalutamide 40mg capsules/tablets
实验性的：CCS1477 Monotherapy - Solid tumours

CCS1477 expansion phase in patients with advanced solid tumours with molecular markers which may indicate potential for response to p300/CBP inhibition
药品：CCS1477

Capsules, oral
实验性的：CCS1477 and darolutamide, combination dose finding and expansion - mCRPC

CCS1477 plus darolutamide in patients with mCRPC
药品：CCS1477

Capsules, oral

药品：Darolutamide

300mg tablets
实验性的：CCS1477 and olaparib, combination dose finding and expansion - mCRPC and metastatic breast cancer

CCS1477 plus olaparib in patients with mCRPC or metastatic breast cancer.
药品：CCS1477

Capsules, oral

药品：Olaparib

150mg tablets
实验性的：CCS1477 and atezolizumab, combination dose finding and expansion - non-small cell lung cancer

CCS1477 plus atezolizumab in patients with non-small cell lung cancer
药品：CCS1477

Capsules, oral

药品：Atezolizumab

840mg/14ml concentrate for solution for infusion vials

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Withdrawal
大体时间：From signing informed consent until the end of the follow-up period (Up to 363 weeks)

Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study intervention, which does not necessarily have a causal relationship with the treatment. Serious AE (SAE) was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs were defined as those events with onset dates/time occurring after study intervention administration or events that worsen after study intervention administration. TEAEs included serious TEAEs and non-serious TEAEs. Number of participants with TEAEs leading to withdrawal of study intervention was also reported.
From signing informed consent until the end of the follow-up period (Up to 363 weeks)
Number of Participants With Worst Shift in Laboratory Data-Hematology According to Common Terminology Criteria for Adverse Events (CTCAE)-Version 5 Grades
大体时间：From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)

Adverse events were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, and Grade 5 = death related to the adverse event. Number of participants with worst shift in hematology according to Common Terminology Criteria for Adverse Events (CTCAE) grades were reported.
From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)
Number of Participants With Worst Shift in Laboratory Data-Biochemistry According to Common Terminology Criteria for Adverse Events (CTCAE)-Version 5 Grades
大体时间：From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)

Adverse events were graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0, where Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = life-threatening, and Grade 5 = death related to the adverse event. Number of participants with worst shift in biochemistry according to Common Terminology Criteria for Adverse Events (CTCAE) grades were reported.
From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)
Number of Participants With Clinically Significant Change From Baseline in Laboratory Parameters - Urinalysis
大体时间：From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)

The urinalysis measurements included glucose, protein and blood. Number of participants with clinically significant changes from baseline in urinalysis values were reported. Clinically Significance was decided by investigator.
From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)
Number of Participants With Clinically Significant Change From Baseline in Vital Signs
大体时间：From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)

The vital signs measurements included blood pressure, heart rate, respiration rate and temperature. Number of participants with clinically significant changes from baseline in vital signs values were reported. Clinically Significance was decided by investigator.
From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)
Number of Participants With Worst Shift in QTcF According to Common Terminology Criteria for Adverse Events (CTCAE)-Version 5 Grades
大体时间：From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles)

Twelve-lead Electrocardiograms (ECGs) were obtained after the participant was in semi-supine for 5 minutes. Three ECGs were taken at each timepoint at about 1-minute intervals. QTcF was calculated using the Fridericia formula: QTcF = QT ÷ RR^(1/3), where QT is the measured QT interval in milliseconds and RR is the interval between two consecutive R waves on the ECG expressed in seconds. It was categorized as less than equal to (<=) 450 milliseconds (msec), more than (>) 450 to <=480 msec, > 480 to <= 500 msec and > 500 msec.
From first dose of study drug in Cycle 1 up to and including 28 days after last dose of study intervention (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles)

次要结果测量

结果测量
措施说明
大体时间
Best Percentage Change From Baseline in Prostate Specific Antigen (PSA) Response in Participants With Metastatic Castration Resistant Prostate Cancer (mCRPC)
大体时间：At Baseline - Cycle 1 - Day 1, Day 8, Day 15, Day 22 and Day 1 of every cycle from cycle 2 onwards until treatment discontinuation (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)

Best percentage change from baseline was defined as the largest percentage reduction in PSA levels or the smallest percentage increase in PSA levels in the absence of a reduction.
At Baseline - Cycle 1 - Day 1, Day 8, Day 15, Day 22 and Day 1 of every cycle from cycle 2 onwards until treatment discontinuation (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles.)
Number of Participants With CTC Response
大体时间：From Baseline - Day 1 Cycle 1 (Predose), Day 1 Cycle 2, Day 1 Cycle 3, Day 1 Cycle 5 up to disease progression or treatment discontinuation (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles)

CTC response was defined as a change from unfavourable (five or more cells per 7.5 mL of blood) at baseline to favourable (four or fewer cells per 7.5 mL) post treatment. Number of participants with overall response were reported. A participant was determined as having an overall CTC response if they had at least one post baseline assessment of 'CTC response'.
From Baseline - Day 1 Cycle 1 (Predose), Day 1 Cycle 2, Day 1 Cycle 3, Day 1 Cycle 5 up to disease progression or treatment discontinuation (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles)
Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
大体时间：From day of study intervention in Cycle 1 until progression or censoring date in the absence of progression (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles)

Objective response is defined as any participant with measurable disease who has a best overall response of Partial Response (PR) or Complete Response (CR). CR is defined as the disappearance of all Target Lesions (TLs) since baseline. PR is defined as At least a 30% decrease in the sum of diameters of TLs, taking as reference the baseline sum of diameters.
From day of study intervention in Cycle 1 until progression or censoring date in the absence of progression (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles)
Radiological Progression Free Survival (rPFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
大体时间：From day of study intervention in Cycle 1 until progression or censoring date in the absence of progression (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles)

Radiological progression free survival (rPFS) was defined as the time from the start of treatment with CCS1477 in Cycle 1 until the earliest objective disease progression defined by RECIST 1.1, Prostate Cancer Clinical Trial Working Group 3 (PCWG-3) bone progression or death by any cause in the absence of progression, regardless of whether the participants withdraws from study medication or receives another anti-cancer therapy prior to progression. Kaplan - Meier estimate was used to calculate the rPFS.
From day of study intervention in Cycle 1 until progression or censoring date in the absence of progression (Up to 363 weeks) (Cycle length was 4 weeks for Cycles 1-6 and 6 weeks for Cycle 7 and subsequent cycles)
Overall Survival (OS)
大体时间：From start of treatment until death (Up to 363 weeks)

Overall survival is defined as the time from the start of treatment with CCS1477 in Cycle 1 until death due to any cause.
From start of treatment until death (Up to 363 weeks)
Maximum Observed Plasma Concentration (Cmax)
大体时间：Cycle 1 Day 1 and Cycle 2 Day 3 (Cycle length was 4 weeks)

Cmax was obtained directly from concentration versus time curve.
Cycle 1 Day 1 and Cycle 2 Day 3 (Cycle length was 4 weeks)
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-24)
大体时间：Cycle 1 Day 1 and Cycle 2 Day 3 (Cycle length was 4 weeks)

AUC0-24 is defined as the area under the concentration-time curve (AUC) from time zero (= dosing time) to 24 hours. AUC0-24 was calculated using the mixed log-linear trapezoidal rule.
Cycle 1 Day 1 and Cycle 2 Day 3 (Cycle length was 4 weeks)

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

CellCentric Ltd.

调查人员

  • 首席研究员：Johann de Bono, MD、Royal Marsden NHS Foundation Trust

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)

2018年7月23日

初级完成 (实际的)

2025年7月6日

研究完成 (实际的)

2025年7月6日

研究注册日期

首次提交

2018年6月4日

首先提交符合 QC 标准的

2018年6月14日

首次发布 (实际的)

2018年6月26日

研究记录更新

最后更新发布 (实际的)

2026年9月25日

上次提交的符合 QC 标准的更新

2026年9月1日

最后验证

2026年7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

  • CCS1477-01

计划个人参与者数据 (IPD)

计划共享个人参与者数据 (IPD)？

不

药物和器械信息、研究文件

研究美国 FDA 监管的药品

是的

研究美国 FDA 监管的设备产品

不

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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