A Study With Tasquinimod Treating Patients With Hepatocellular, Ovarian, Renal Cell and Gastric Cancers

Inclusion Criteria - All Patients:

• Able and willing to provide written informed consent and to comply with the study protocol and procedures.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1.
• Life expectancy greater than 3 months in the Investigator's opinion.
• Disease progression during or after previous cancer treatment.
• Measurable disease as per Response Evaluation Criteria in Solid Tumours (RECIST) Criteria (v1.1).
• The following time must have elapsed between previous therapy for cancer and first administration of tasquinimod:
• At least 2 weeks since previous systemic targeted therapy with small molecule inhibitors, which included any tyrosine-kinase inhibitor.
• At least 4 weeks since the last dose of systemic anti-cancer therapy other than targeted therapy, which included cytotoxic agents, monoclonal antibody therapy, immunotherapy and prior radiotherapy.
• At least 1 week since prior hormonal therapy.
• At least 3 months since prior interferon therapy.
• Recovery to Grade 1 from the effects (excluding alopecia) of any prior therapy for their malignancies.
• At least 4 weeks since any major surgery or open biopsy and 7 days since a core biopsy before first study treatment.
• Adequate renal function:
• Creatinine ≤1.5 times upper limit of normal (ULN) or calculated creatinine clearance (CrCl) using the Cockcroft Gault formula ≥60 mL/min, or CrCl ≥60 mL/min.
• Adequate hepatic function:
• Serum bilirubin ≤1.5 mg/dL (≤25 μmol/L) for ovarian carcinoma, renal cell carcinoma and gastric carcinoma, serum bilirubin ≤3 mg/dL (≤50 μmol/L) for hepatocellular carcinoma cohorts.
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 x ULN (≤5 x ULN if liver lesions were present i.e. liver metastasis or primary tumour of the liver for hepatocellular carcinoma cohort).
• Adequate bone marrow function:
• Absolute neutrophil count (ANC) ≥1.5 x 10^9/L.
• Platelets ≥50 x 10^9/L.
• Haemoglobin ≥90 g/L.
• Adequate coagulation tests: international normalised ratio (INR) ≤1.5 x ULN.
• Able to swallow capsules.
• For women of childbearing potential, a negative pregnancy test must have been documented prior to first administration of study treatment.
• For women who were not postmenopausal (12 months of amenorrhea) or surgically sterile (absence of ovaries and/or uterus): agreement to use adequate methods of contraception (e.g. hormonal implants, combined oral contraceptives, vasectomised partner), during the treatment period and for at least 3 months after the last dose of study treatment.
• For men: agreement to use a barrier method of contraception during the treatment period and for at least 3 months after the last dose of study treatment.

Inclusion Criteria - Hepatocellular Carcinoma Cohort:

• Histologically confirmed and documented hepatocellular carcinoma (excluding fibrolamellar carcinoma).
• Barcelona Clinic Liver Cancer (BCLC) stage C or BCLC stage B not amenable to locoregional therapy or refractory to locoregional therapy.
• Liver mass measuring at least 2 cm with characteristic vascularisation seen on either triphasic computed tomography (CT) scan or Magnetic Resonance Imaging (MRI) with gadolinium.
• At least one measurable or evaluable lesion that was viable (i.e. vascularised), and had not been previously treated with locoregional therapy. A lesion that had been previously treated qualified as a measurable or evaluable lesion if there was demonstrable progression following locoregional therapy.
• Child-Pugh A Class only.
• Previously treated with sorafenib. Patients may have experienced radiographically documented disease progression during sorafenib therapy or after discontinuation of sorafenib therapy.
• The patient had received sorafenib as the most recent systemic therapeutic intervention (any hepatic locoregional therapy that had been administered prior to sorafenib was allowed, but not following sorafenib; radiat