Advanced Solid Tumors, Metastatic Breast Cancer, Metastatic Castration-Resistant Prostate Cancer, Non-small Cell Lung Cancer
Conditions
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.
Interventions
DRUGCCS1477
Capsules, oral
DRUGAbiraterone acetate
Abiraterone acetate 500mg tablets plus prednisone/prednisolone
DRUGEnzalutamide
Enzalutamide 40mg capsules/tablets
DRUGDarolutamide
300mg tablets
DRUGOlaparib
150mg tablets
DRUGAtezolizumab
840mg/14ml concentrate for solution for infusion vials
Sponsors
CellCentric Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The RP2D/MTD dose will be determined in Part A. Parts B-H will run in parallel after the completion of Part A.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-related adverse events | Up to 12 months | Treatment-related adverse events and serious adverse events |
| Laboratory assessments | Up to 12 months | Clinical chemistry and haematology assessments |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective response rate (ORR) | Up to 12 months | * malignant soft tissue response rate (Response Evaluation Criteria in Solid Tumours \[RECIST\] v1.1) * metastatic bone disease status (PCWG-3 bone scan criteria) |
| Radiological progression-free survival (rPFS) | Up to 12 months | Defined as the time from start of treatment until objective disease progression as defined by RECIST 1.1 or PCWG-3 or death |
| PSA response | Up to 12 months | PSA response as defined by Prostate Cancer Clinical Trial Working Group 3 (PCWG-3) |
| Cmax of CCS1477 | Up to 30 days after first dose of CCS1477 | Maximum observed plasma concentration (Cmax) of CCS1477 |
| AUC of CCS1477 | Up to 30 days after first dose of CCS1477 | Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable concentration of CCS1477 |
| CTC response | Up to 12 months | CTC response defined as a change from unfavourable (five or more cells) at baseline to favourable (four or fewer cells) post treatment |
Countries
France, Netherlands, Spain, Sweden, United Kingdom, United States
Outcome results
None listed