study to evaluate ccs1477 in advanced tumours

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

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.


Eligibility criteria:
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