Results
diarrhoea, nausea, study-drug-related TEAEs, HGG, vomiting, Treatment-emergent adverse
DISEASE, DISEASE PROGRESSION, SOLID TUMOUR
Fifty-four patients were enrolled and treated at 5 investigational sites in the United Kingdom and Spain. Study design included two phases: Dose-escalation phase (DE) and Expansion Phase (EP) at the Maximum tolerated dose determined at the DE. No patient withdrew due to an AE or a serious AE (SAE) in either the dose escalation or expansion phases of the study. Thirty-two patients (15 with HGG, 17 with other advanced solid tumours) were enrolled in the DE of the study. Twenty-five (78.1%) patients were followed up until disease progression, 5 (15.6%) patients withdrew consent, and 2 (6.3%) discontinued treatment due to an investigator decision. Twenty-two patients (12 with HGG, 10 with other advanced solid tumours) were enrolled in the expanded safety cohorts, and all patients received study drug. In the expansion cohort, only 1 patient (5.4%) discontinued due to non-compliance with study drug, while the remaining 31 (95.5%) discontinued due to disease progression.Patient baseline characteristics are listed in Table Thirty-two patients were included in the DE at dose levels ranging from 500 to 16,000 mg (daily, p.o.: Fig. Treatment compliance was defined as taking ≥80% of the intended dose of 2-OHOA. During cycle 1, 38 (70.4%) patients were deemed treatment compliant, including 24 (75%) patients during the dose-escalation phase and 14 (63.6%) patients in the expanded safety cohorts. Across all treatment cycles, 33 (61.1%) patients were treatment compliant, including 22 (60.8%) during the dose-escalation phase and 11 (50%) in the expanded safety cohorts.Fifty-four patients were included in the safety analysis. All patients experienced at least 1 treatment-emergent AEs (TEAE) during the study. The most common TEAEs were diarrhoea (31 [57.4%]), nausea (23 [42.6%]) and vomiting (18 [33.3%]) (Table Treatment-emergent adverse events occurring in >10% of patients in total (safety analysis set) by CTCAE grade.Forty-two (77.8%) patients experienced at least one study-drug-related TEAE. The most frequent study-drug-related TEAEs were diarrhoea (28 [51.8%]), nausea (18 [33.3%]), and vomiting (17 [31.5%]) (Table Increases in alkaline phosphatase, ALT, AST, urea and total bilirubin to above normal range were noted in 10–50% of patients, but there was no apparent dose effect and shifts were typical of a patient’s disease. There was no apparent dose effect on fasting blood lipid parameters or serum amylase. There were no clinically significant study-drug-related ECGs changes.PK findings showed that 2-OHOA was quantifiable across the dose range investigated (Fig. 