NCT05495295

First-in-human Trial of PhOx430, a First-in-class Acetylglucosaminyltransferase V Inhibitor, in Advanced Solid Tumours

An Adaptive First-in-human Trial of PhOx430, a First-in-class Acetylglucosaminyltransferase V Inhibitor, in Patients With Advanced Solid Tumours (PhAST Trial)

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 149 (estimated)
• Sponsor: Phost'In Therapeutics · Industry
• Sex: All
• Age: 18 Years – 80 Years
• Healthy volunteers: Not accepted

Summary

The PhAST Trial is an adaptive first-in-human clinical trial of the acetylglucosaminyltransferase V inhibitor PhOx430 in patients with advanced solid tumours conceived and designed with the contribution of the Gianni Bonadonna Foundation, a non-profit academic research institution aimed at promoting therapeutic innovation in oncology.. The trial includes two parts, a dose escalation phase which will enroll patients with non-selected tumour types, followed by a cohort expansion phase in selected tumour types.

Detailed description

The PhAST Trial is a first-in-human clinical trial of the acetylglucosaminyltransferase V inhibitor PhOx430 in patients with advanced solid tumours. The trial includes two parts, a dose escalation phase (part I) which will enroll patients with non-selected tumour types, followed by a cohort expansion phase (part II) in selected tumour types. POPULATION: Adult patients with advanced or metastatic solid malignancies with radiologically documented progression on a previous line of treatment and for which effective treatment options do not exist. DOSE ESCALATION'S PRIMARY OBJECTIVE: To determine the Maximal Tolerated Dose (MTD) and Recommended Phase II Dose (RP2D) of PhOx430 in patients with advanced solid tumours DOSE ESCALATION'S SECONDARY OBJECTIVE: 1. to determine the safety and tolerability profile of PhOx430 at increasing dose levels; 2. to characterize the pharmacokinetic (PK) profile of PhOx430, including food effect on drug disposition; 3. to evaluate the antitumour activity of PhOx430. DOSE ESCALATION'S EXPLORATORY OBJECTIVE: 4. to characterize the pharmacodynamics (PD) effect of PhOx430 on blood, urine and tumour samples collected before and after treatment; 5. to identify predictive response biomarkers by profiling responsive patterns. DOSE EXPANSIONS' PRIMARY OBJECTIVE: To better characterize the safety and tolerability profile of PhOx430 given at the RP2D in three cohorts of patients affected by 1) glioblastoma multiforme (GBM), 2) triple-negative breast cancer, and 3) selected types of solid tumours. DOSE EXPANSION'S SECONDARY OBJECTIVE: 1. to characterize the pharmacokinetic (PK) profile of PhOx430 at the RP2D. 2. to evaluate the antitumour activity of PhOx430 in the specific tumour types selected for the dose expansion cohorts. DOSE EXPANSIONS' EXPLORATORY OBJECTIVE: 3. to characterize the pharmacodynamic (PD) effect of PhOx430 on blood, urine and tumour samples collected before and after treatment; 4. to identify predictive response biomarkers by profiling responsive patterns. STUDY DESIGN AND TREATMENT PLAN: Dose Escalation Phase - STEP 1-2: a standard 3 + 3 design will be followed. PhOx430 will be administered orally twice a day (bid), at a 12-hour interval, continuously in cycles of 21 days. At each dose level (DL), at least three patients will be included and the first patient will be observed for at least 21 days before enrolling the following two. Dose Escalation Phase - STEP 3 (Dosing-optimization Cohort): The implementation of this Dosing-optimization cohort (Step 3) was decided by the Protocol Steering Committee (PSC) based on clinical and pharmacokinetic data obtained in Steps 1 and 2. Six patients will be enrolled, who will be administered a flat dose of PhOx430 (1,200 mg by patients weighing ≥ 50 kg and of 600 mg by patients weighing \< 50 kg) orally thrice a day (tid) for 21 days, and then, starting from day 22, four times a day (qid), continuously in cycles of 21 days. The first patient will be observed after treatment start for at least 21 days before enrolling the following two. After the third patient is observed for 21 days after treatment start, three additional patients will be enrolled without waiting time between them. In case the daily dose tested with the tid schedule is not deemed safe, the flat dose of PhOx430 will be tested twice a day (bid). Cohort Expansion Phase: in the cohort expansion phase, the safety profile of PhOx430 will be further characterized by testing the RP2D in three parallel cohorts of patients affected by glioblastoma multiforme (GBM) (cohort 1), triple-negative breast cancer (TNBC) (cohort 2), and solid tumour types selected by the Protocol Steering Committee (PSC) on the basis of preclinical pharmacological data and of the antitumour activity observed during the Dose Escalation Phase if any (cohort 3), respectively. Cycles will be of 21 days. ESTIMATED TRIAL DURATION and SAMPLE SIZE: Dose Escalation Phase Step 1,2,3: approximately 1.5 years Expansion Phase: approximately 1.5 years. The end of trial is defined as 30 days after the last dose of the last enrolled patient. The following numbers of patients are foreseen: up to 149 patients.

Conditions

• Malignant Tumor
• Advanced Solid Tumor
• Glioblastoma Multiforme
• Metastatic Cancer

Interventions

Type	Name	Description
DRUG	PhOx430	A standard 3 + 3 design will be followed. PhOx430 will be administered orally twice a day (bid), at a 12-hour interval, continuously in cycles of 21 days. At each dose level (DL), three patients will be included and the first patient will be observed for at least 21 days before enrolling the following two. Three additional patients will be enrolled at each DL if a DLT is observed in the first three patients. A maximum of 4 increasing Dose Levels are foreseen (10, 20, 40 and 70 mg/kg/day), and PhOx430 will be administered in two doses at a 12-hour interval.
DRUG	PhOx430	The implementation of this cohort (Step 3) was decided by the Protocol Steering Committee (PSC) based on clinical and pharmacokinetic data obtained in Steps 1 and 2. Six patients will be enrolled, who will receive PhOx430 orally thrice a day (tid) at a -6-hour interval over 12 hours for 21 days, and then, starting from day 22, four times a day (qid) at a 4-hour interval over 12 hours, continuously in cycles of 21 days. PhOx430 will be taken in single doses of 1,200 mg to patients weighing ≥ 50 kg and of 600 mg to patients weighing \< 50 kg, with no requirement for a full or empty stomach. The first patient will be observed after treatment start for at least 21 days before enrolling the following two. After the third patient is observed for 21 days after treatment start, 3 additional patients will be enrolled without waiting time between them. If the daily dose tested with the tid schedule is not deemed safe, the flat dose will be tested twice a day (bid) at a 12-hour interval.

Timeline

• Start date: 2022-07-18
• Primary completion: 2024-11-04
• Completion: 2027-07-31
• First posted: 2022-08-10
• Last updated: 2025-04-08

Locations

4 sites across 2 countries: France, Italy