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.

CCS1477-01

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.

2018-07-23

2024-03-01

2024-03-01

Recruiting

Early phase I

350

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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'The RP2D/MTD dose will be determined in Part A. Parts B-H will run in parallel after the completion of Part A.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 350, 'type': 'ESTIMATED'}}

2024-01-19