Study to Evaluate CCS1477 in Advanced Tumours

NCT ID: NCT03568656

Last Updated: 2025-08-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

220 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-07-23

Study Completion Date

2025-07-06

Brief Summary

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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.

Detailed Description

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Conditions

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Metastatic Castration-Resistant Prostate Cancer Metastatic Breast Cancer Non-small Cell Lung Cancer Advanced Solid Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

The RP2D/MTD dose will be determined in Part A. Parts B-H will run in parallel after the completion of Part A.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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CCS1477 dose escalation - mCRPC

CCS1477 monotherapy in patients with mCRPC

Group Type EXPERIMENTAL

CCS1477

Intervention Type DRUG

Capsules, oral

CCS1477 expansion phase - mCRPC

CCS1477 monotherapy in patients with mCRPC

Group Type EXPERIMENTAL

CCS1477

Intervention Type DRUG

Capsules, oral

CCS1477 and abiraterone acetate, combination dose finding and expansion - mCRPC

CCS1477 plus abiraterone acetate in patients with mCRPC

Group Type EXPERIMENTAL

CCS1477

Intervention Type DRUG

Capsules, oral

Abiraterone acetate

Intervention Type DRUG

Abiraterone acetate 500mg tablets plus prednisone/prednisolone

CCS1477 and enzalutamide, combination dose finding and expansion - mCRPC

CCS1477 plus enzalutamide in patients with mCRPC

Group Type EXPERIMENTAL

CCS1477

Intervention Type DRUG

Capsules, oral

Enzalutamide

Intervention Type DRUG

Enzalutamide 40mg capsules/tablets

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

Group Type EXPERIMENTAL

CCS1477

Intervention Type DRUG

Capsules, oral

CCS1477 and darolutamide, combination dose finding and expansion - mCRPC

CCS1477 plus darolutamide in patients with mCRPC

Group Type EXPERIMENTAL

CCS1477

Intervention Type DRUG

Capsules, oral

Darolutamide

Intervention Type DRUG

300mg tablets

CCS1477 and olaparib, combination dose finding and expansion - mCRPC and metastatic breast cancer

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

Group Type EXPERIMENTAL

CCS1477

Intervention Type DRUG

Capsules, oral

Olaparib

Intervention Type DRUG

150mg tablets

CCS1477 and atezolizumab, combination dose finding and expansion - non-small cell lung cancer

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

Group Type EXPERIMENTAL

CCS1477

Intervention Type DRUG

Capsules, oral

Atezolizumab

Intervention Type DRUG

840mg/14ml concentrate for solution for infusion vials

Interventions

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CCS1477

Capsules, oral

Intervention Type DRUG

Abiraterone acetate

Abiraterone acetate 500mg tablets plus prednisone/prednisolone

Intervention Type DRUG

Enzalutamide

Enzalutamide 40mg capsules/tablets

Intervention Type DRUG

Darolutamide

300mg tablets

Intervention Type DRUG

Olaparib

150mg tablets

Intervention Type DRUG

Atezolizumab

840mg/14ml concentrate for solution for infusion vials

Intervention Type DRUG

Eligibility Criteria

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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


* 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


* 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


* 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


* 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.


* Clinically significant cardiac abnormalities


* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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CellCentric Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Johann de Bono, MD

Role: PRINCIPAL_INVESTIGATOR

Royal Marsden NHS Foundation Trust

Locations

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Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

Institute Bergonie

Bordeaux, , France

Site Status

Hôpital Europeen Georges Pompidou

Paris, , France

Site Status

Institute Gustave Roussy

Villejuif, , France

Site Status

Netherlands Cancer Institute (NKI)

Amsterdam, , Netherlands

Site Status

Hospital Vall d'Hebron, VHIO

Barcelona, , Spain

Site Status

START CIOCC Hospital Universitario HM

Madrid, , Spain

Site Status

Karolinska Institute

Stockholm, , Sweden

Site Status

Belfast City Hospital

Belfast, , United Kingdom

Site Status

Queen Elizabeth Hospital Cancer Centre

Birmingham, , United Kingdom

Site Status

Cambridge University Hospital

Cambridge, , United Kingdom

Site Status

Edinburgh Cancer Centre Western General Hospital

Edinburgh, , United Kingdom

Site Status

The Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Site Status

Leicester Royal Infirmary

Leicester, , United Kingdom

Site Status

The Christie Hospital

Manchester, , United Kingdom

Site Status

Freeman Hospital

Newcastle, , United Kingdom

Site Status

University Hospital Southampton

Southampton, , United Kingdom

Site Status

Royal Marsden Hospital

Sutton, , United Kingdom

Site Status

Countries

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United States France Netherlands Spain Sweden United Kingdom

References

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Caligiuri M, Williams GL, Castro J, Battalagine L, Wilker E, Yao L, Schiller S, Toms A, Li P, Pardo E, Graves B, Azofeifa J, Chicas A, Herbertz T, Lai M, Basken J, Wood KW, Xu Q, Guichard SM. FT-6876, a Potent and Selective Inhibitor of CBP/p300, is Active in Preclinical Models of Androgen Receptor-Positive Breast Cancer. Target Oncol. 2023 Mar;18(2):269-285. doi: 10.1007/s11523-023-00949-7. Epub 2023 Feb 24.

Reference Type DERIVED
PMID: 36826464 (View on PubMed)

Eickhoff N, Bergman AM, Zwart W. Homing in on a Moving Target: Androgen Receptor Cistromic Plasticity in Prostate Cancer. Endocrinology. 2022 Oct 11;163(11):bqac153. doi: 10.1210/endocr/bqac153.

Reference Type DERIVED
PMID: 36125208 (View on PubMed)

Other Identifiers

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CCS1477-01

Identifier Type: -

Identifier Source: org_study_id

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