Study to Evaluate CCS1477 in Advanced Tumours

CellCentric

Status and phase: Completed; Phase 2; Phase 1

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

Treatments: Drug: Olaparib; Drug: Atezolizumab; Drug: CCS1477; Drug: Enzalutamide; Drug: Darolutamide; Drug: Abiraterone acetate

Study type: Interventional

Funder types: Industry

Identifiers

NCT03568656

CCS1477-01

Details and patient eligibility

About

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.

Enrollment: 220 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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220 participants in 8 patient groups

CCS1477 dose escalation - mCRPC

Experimental group

Description:

CCS1477 monotherapy in patients with mCRPC

Treatment:

Drug: CCS1477

CCS1477 expansion phase - mCRPC

Experimental group

Description:

CCS1477 monotherapy in patients with mCRPC

Treatment:

Drug: CCS1477

CCS1477 and abiraterone acetate, combination dose finding and expansion - mCRPC

Experimental group

Description:

CCS1477 plus abiraterone acetate in patients with mCRPC

Treatment:

Drug: Abiraterone acetate

Drug: CCS1477

CCS1477 and enzalutamide, combination dose finding and expansion - mCRPC

Experimental group

Description:

CCS1477 plus enzalutamide in patients with mCRPC

Treatment:

Drug: Enzalutamide

Drug: CCS1477

CCS1477 Monotherapy - Solid tumours

Experimental group

Description:

CCS1477 expansion phase in patients with advanced solid tumours with molecular markers which may indicate potential for response to p300/CBP inhibition

Treatment:

Drug: CCS1477

CCS1477 and darolutamide, combination dose finding and expansion - mCRPC

Experimental group

Description:

CCS1477 plus darolutamide in patients with mCRPC

Treatment:

Drug: Darolutamide

Drug: CCS1477

CCS1477 and olaparib, combination dose finding and expansion - mCRPC and metastatic breast cancer

Experimental group

Description:

CCS1477 plus olaparib in patients with mCRPC or metastatic breast cancer.

Treatment:

Drug: CCS1477

Drug: Olaparib

CCS1477 and atezolizumab, combination dose finding and expansion - non-small cell lung cancer

Experimental group

Description:

CCS1477 plus atezolizumab in patients with non-small cell lung cancer

Treatment:

Drug: CCS1477

Drug: Atezolizumab