Study to Evaluate CCS1477 in Advanced Tumours

Non-small Cell Lung Cancer Clinical Trial

Official title:

An Open-label Phase I/IIa Study to Evaluate the Safety and Efficacy of CCS1477 as Monotherapy and in Combination, in Patients With Advanced Solid/Metastatic Tumours.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03568656
• Other study ID #: CCS1477-01
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: July 23, 2018
• Est. completion date: March 2024

Study information

• Verified date: April 2023
• Source: CellCentric Ltd.
• Contact: Tomasz Knurowski, MD, MFPM
• Phone: 07882 871299
• Email: Tomasz.Knurowski[@]cellcentric.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 350
• Est. completion date: March 2024
• Est. primary completion date: March 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Carcinoma, Non-Small-Cell Lung
• Metastatic Breast Cancer
• Metastatic Castration-Resistant Prostate Cancer
• Non-small Cell Lung Cancer

Intervention

Drug:
• CCS1477
Capsules, oral
• Abiraterone acetate
Abiraterone acetate 500mg tablets plus prednisone/prednisolone
• Enzalutamide
Enzalutamide 40mg capsules/tablets
• Darolutamide
300mg tablets
• Olaparib
150mg tablets
• Atezolizumab
840mg/14ml concentrate for solution for infusion vials

Locations

Country	Name	City	State
France	Institute Bergonie	Bordeaux
France	Hôpital Europeen Georges Pompidou	Paris
France	Institute Gustave Roussy	Villejuif
Netherlands	Netherlands Cancer Institute (NKI)	Amsterdam
Netherlands	Erasmus MC Institute	Rotterdam
Spain	Hospital Vall d'Hebron, VHIO	Barcelona
Spain	START CIOCC Hospital Universitario HM	Madrid
Spain	INCLIVA Biomedical Research Institute	Valencia
Sweden	Karolinska Institute	Stockholm
United Kingdom	Belfast City Hospital	Belfast
United Kingdom	Queen Elizabeth Hospital Cancer Centre	Birmingham
United Kingdom	Cambridge University Hospital	Cambridge
United Kingdom	Edinburgh Cancer Centre Western General Hospital	Edinburgh
United Kingdom	The Beatson West of Scotland Cancer Centre	Glasgow
United Kingdom	Leicester Royal Infirmary	Leicester
United Kingdom	The Christie Hospital	Manchester
United Kingdom	Freeman Hospital	Newcastle
United Kingdom	University Hospital Southampton	Southampton
United Kingdom	Royal Marsden Hospital	Sutton
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	New York-Presbyterian Hospital/Weill Cornell Medical Center	New York	New York
United States	Thomas Jefferson University, Sidney Kimmel Cancer Center	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
CellCentric Ltd.

Countries where clinical trial is conducted

United States,  France,  Netherlands,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of treatment-related adverse events	Treatment-related adverse events and serious adverse events	Up to 12 months
Primary	Laboratory assessments	Clinical chemistry and haematology assessments	Up to 12 months
Secondary	PSA response	PSA response as defined by Prostate Cancer Clinical Trial Working Group 3 (PCWG-3)	Up to 12 months
Secondary	CTC response	CTC response defined as a change from unfavourable (five or more cells) at baseline to favourable (four or fewer cells) post treatment	Up to 12 months
Secondary	Objective response rate (ORR)	malignant soft tissue response rate (Response Evaluation Criteria in Solid Tumours [RECIST] v1.1); metastatic bone disease status (PCWG-3 bone scan criteria)	Up to 12 months
Secondary	Radiological progression-free survival (rPFS)	Defined as the time from start of treatment until objective disease progression as defined by RECIST 1.1 or PCWG-3 or death	Up to 12 months
Secondary	AUC of CCS1477	Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable concentration of CCS1477	Up to 30 days after first dose of CCS1477
Secondary	Cmax of CCS1477	Maximum observed plasma concentration (Cmax) of CCS1477	Up to 30 days after first dose of CCS1477