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

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.

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