Study to Evaluate CCS1477 in Advanced Tumours

NCT03568656 | Completed Phase 1 Results FDA Drug

• 1 other identifier: CCS1477-01
• Study Type: interventional
• Target: 219
• Locations: 6 countries
• Sites: 19

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (6)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Withdrawal

  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

  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

  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

  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

  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

  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)

Secondary Outcomes (7)

• Best Percentage Change From Baseline in Prostate Specific Antigen (PSA) Response in Participants With Metastatic Castration Resistant Prostate Cancer (mCRPC)

  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

  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

  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

  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)

  From start of treatment until death (Up to 363 weeks)

Study Arms (8)

CCS1477 dose escalation - mCRPC

EXPERIMENTAL

CCS1477 monotherapy in patients with mCRPC

Drug: CCS1477

CCS1477 expansion phase - mCRPC

EXPERIMENTAL

CCS1477 monotherapy in patients with mCRPC

Drug: CCS1477

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

EXPERIMENTAL

CCS1477 plus abiraterone acetate in patients with mCRPC

Drug: CCS1477; Drug: Abiraterone acetate

CCS1477 and enzalutamide, combination dose finding and expansion - mCRPC

EXPERIMENTAL

CCS1477 plus enzalutamide in patients with mCRPC

Drug: CCS1477; Drug: Enzalutamide

CCS1477 Monotherapy - Solid tumours

EXPERIMENTAL

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

Drug: CCS1477

CCS1477 and darolutamide, combination dose finding and expansion - mCRPC

EXPERIMENTAL

CCS1477 plus darolutamide in patients with mCRPC

Drug: CCS1477; Drug: Darolutamide

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

EXPERIMENTAL

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

Drug: CCS1477; Drug: Olaparib

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

EXPERIMENTAL

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

Drug: CCS1477; Drug: Atezolizumab

Interventions

CCS1477 DRUG

Capsules, oral

CCS1477 Monotherapy - Solid tumours; CCS1477 and abiraterone acetate, combination dose finding and expansion - mCRPC; CCS1477 and atezolizumab, combination dose finding and expansion - non-small cell lung cancer; CCS1477 and darolutamide, combination dose finding and expansion - mCRPC; CCS1477 and enzalutamide, combination dose finding and expansion - mCRPC; CCS1477 and olaparib, combination dose finding and expansion - mCRPC and metastatic breast cancer; CCS1477 dose escalation - mCRPC; CCS1477 expansion phase - mCRPC

Abiraterone acetate DRUG

Abiraterone acetate 500mg tablets plus prednisone/prednisolone

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

Enzalutamide DRUG

Enzalutamide 40mg capsules/tablets

CCS1477 and enzalutamide, combination dose finding and expansion - mCRPC

Darolutamide DRUG

300mg tablets

CCS1477 and darolutamide, combination dose finding and expansion - mCRPC

Olaparib DRUG

150mg tablets

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

Atezolizumab DRUG

840mg/14ml concentrate for solution for infusion vials

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• CellCentric Ltd.: lead

Study Sites (19)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Thomas Jefferson University, Sidney Kimmel Cancer Center

Philadelphia, Pennsylvania, 19107, United States

Location

Institute Bergonie

Bordeaux, 33000, France

Location

Hôpital Europeen Georges Pompidou

Paris, 75015, France

Location

Institute Gustave Roussy

Villejuif, 94805, France

Location

Netherlands Cancer Institute (NKI)

Amsterdam, 1066 CX, Netherlands

Location

Hospital Vall d'Hebron, VHIO

Barcelona, 08035, Spain

Location

START CIOCC Hospital Universitario HM

Madrid, 28050, Spain

Location

Karolinska Institute

Stockholm, 171 76, Sweden

Location

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

Location

Queen Elizabeth Hospital Cancer Centre

Birmingham, B15 2TH, United Kingdom

Location

Cambridge University Hospital

Cambridge, CB2 0QQ, United Kingdom

Location

Edinburgh Cancer Centre Western General Hospital

Edinburgh, EH4 2XU, United Kingdom

Location

The Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Leicester Royal Infirmary

Leicester, LE1 5WW, United Kingdom

Location

The Christie Hospital

Manchester, M20 4BX, United Kingdom

Location

Freeman Hospital

Newcastle, NE7 7DN, United Kingdom

Location

University Hospital Southampton

Southampton, SO16 6YD, United Kingdom

Location

Royal Marsden Hospital

Sutton, SM2 5NG, United Kingdom

Location

Related Publications (2)

• 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.

  PMID: 36826464 DERIVED

• 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.

  PMID: 36125208 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Carcinoma, Non-Small-Cell Lung

Interventions

CCS1477; Abiraterone Acetate; enzalutamide; darolutamide; olaparib; atezolizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Study Director
• Organization: CellCentric Ltd.

clinical@cellcentric.com

+44 1799 531130

Study Officials

• Johann de Bono, MD

  Royal Marsden NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The RP2D/MTD dose will be determined in Part A. Parts B-H will run in parallel after the completion of Part A.

Study Record Dates

• First Submitted: June 4, 2018
• First Posted: June 26, 2018
• Study Start: July 23, 2018
• Primary Completion: July 6, 2025
• Study Completion: July 6, 2025
• Last Updated: September 25, 2026
• Results First Posted: September 25, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2); SE (1); US (2); FR (3); NL (1); GB (10)