A Trial of CXD101 in Combination With Nivolumab in Patients With Metastatic Microsatellite-Stable Colorectal Cancer (CAROSELL)

Inclusion Criteria:

• Written informed consent
• Biopsy-confirmed MSS, MMR-P CRC. It is acceptable for this test to be performed on the archived primary colorectal cancer tissue and repeat biopsy for MSS testing is not required unless assay not yet performed and insufficient material available
• Previous first and second line treatment (unless contra-indicated) including use of oxaliplatin and irinotecan unless documented intolerance of these
• Measurable disease: longest diameter≥10mm (short axis ≥15mm for nodal lesions)
• Age > 18 years
• Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
• Predicted life expectancy > 3 months
• Adequate organ and bone marrow function: Hb> 10.0g/dL (may be transfused to this level), neutrophils> 1.5x10^9/L and platelets> 100x10^9/L
• Female patients with reproductive potential must have a negative urine and serum pregnancy test prior to starting treatment. Both women of reproductive potential and men must agree to use a medically acceptable method of contraception throughout the treatment period and for 5 months after discontinuation of treatment (i.e., combined oestrogen and progestogen ovulation inhibition; progestogen-only ovulation inhibition; intrauterine device; intrauterine hormone-releasing system; bilateral tubal occlusion; or vasectomised partner). Oral contraception and parenteral hormonal contraceptives (patches, injectables and implants) that may be affected by enzyme-inducing drugs should only be used in combination with a barrier method. All males with partners of childbearing potential or whose partners are pregnant must use barrier contraception for the duration of dosing and for 5 months post-dosing.

Exclusion Criteria:

• Pregnant or breast feeding
• Pre-existing auto-immune conditions
• Medical conditions requiring systemic immunosuppression
• Previous treatment with an HDAC inhibitor or PD-1/PD-L1 inhibitor
• Other chemotherapy, radiotherapy, or investigational therapy within 4 weeks of the Screening /Baseline Assessment
• Unresolved clinically significant toxicity from a previous treatment
• History of recent active chronic inflammatory bowel disease and/or bowel obstruction
• Renal function: Serum creatinine > 1.5 x ULN, or creatinine clearance < 60mL/min (Cockcroft-Gault formula)
• Liver function: AST > 3.0 x ULN; OR total bilirubin > 1.5 x ULN
• Clinically significant myocardial infarction, severe/unstable angina pectoris, congestive heart failure NYHA Class III or IV, or pulmonary disease within 6 months
• Symptomatic brain metastasis, uncontrolled seizure disorder, spinal cord compression, or carcinomatous meningitis
• Clinically significant active infection requiring antibiotic or antiretroviral therapy
• History of malignancy other than MSS CRC, unless there is the expectation that the malignancy has been cured, and tumour specific treatment for the malignancy has not been administered within the previous 5 years
• History of pneumonitis, immune hepatitis or myocarditis, or current uncontrolled thyroid disease
• Current positive serology for Hepatitis B or C virus
• History of any allergy to excipients of the Investigational Medicinal Products (sodium citrate dihydrate, sodium chloride, mannitol, pentetic acid, Polysorbate 80, sodium hydroxide, hydrochloric acid, hydroxypropyl methylcellulose)
• Receipt of any live vaccine 30 days or fewer prior to administration of first dose IMP
• Inability to comply with the study protocol