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

NCT05495295 | Recruiting Phase 1

• 2 other identifiers: PHOX-CLI_0012021-004170-55
• Study Type: interventional
• Target: 149
• Locations: 2 countries
• Sites: 4

Brief 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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• DOSE ESCALATION PRIMARY OUTCOME (Dose Limiting Toxicities (DLTs))

  Dose Limiting Toxicities (DLTs)

  At the end of Cycle 1 and Cycle 2 (each cycle is 21 days)

• DOSE EXPANSION PRIMARY OUTCOME (treatment-emergent Adverse Events)

  Incidence, severity and seriousness of treatment-emergent Adverse Events (AEs)

  Through study completion, up to 5 years

Secondary Outcomes (9)

• DOSE ESCALATION SECONDARY OUTCOME #1 (treatment-emergent Adverse Events)

  Through study completion, up to 5 years

• DOSE ESCALATION SECONDARY OUTCOME #2 (Plasma concentration levels of PhOx430)

  During Cycle1 and Cycle 2 (each cycle is 21 days)

• DOSE ESCALATION SECONDARY OUTCOME #3 (Objective response rate)

  Through dose escalation completion, an average of 1 year

• DOSE EXPANSION SECONDARY OUTCOME #1 (Plasma concentration levels of PhOx430 )

  During Cycle1 and Cycle 2 (each cycle is 21 days)

• DOSE EXPANSION SECONDARY OUTCOME #2 (Objective response rate)

  Through dose expansion completion, an average of 1.5 year

Study Arms (1)

Advanced Solid Tumours

EXPERIMENTAL

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: * Glioblastoma Multiforme (GBM) * Triple Negative Breast Cancer (TNBC) * Selected solid tumours

Drug: PhOx430

Interventions

PhOx430 DRUG

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.

Also known as: Dose Escalation Phase - STEP 1 and STEP 2

Advanced Solid Tumours

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically or cytologically confirmed diagnosis of cancer.
• Dose escalation phase: patients with any solid tumour type or histology.
• Expansion cohort 1: Patients affected by GBM.
• Expansion cohort 2: Patients with triple-negative breast cancer (TNBC), defined as estrogen receptor (ER) negative (\< 1% of nuclei reacting for ER in IHC), progesterone receptor (PgR) negative (\< 1% of nuclei reacting for PgR in IHC), HER2 negative (IHC score = 0 or 1 or ICH score = 2 with FISH negative for HER2 overexpression. If only FISH was performed, negative result for HER2 overexpression).
• Expansion cohort 3: Patients affected by solid tumour types selected by the PSC, on the basis of preclinical pharmacological data and of the antitumour activity observed during the dose escalation phase if any.
• Radiologically documented progressive disease after at least one prior treatment for metastatic/advanced disease.
• Lack of standard effective treatment options.
• Female or male patients of ≥ 18 years and ≤ 80 years
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1. For GBM patients: Karnofsky Performance Status ≥ 50%.
• Recovery from acute reversible toxicities of previous treatment to Grade ≤ 1.
• Tumour tissue accessible for repeated biopsies (except GBM patients).
• For GBM patients: stable dose of corticosteroids for \> 5 days before the baseline MRI scan.
• For non-GBM patients: Measurable disease as defined by Response Evaluation Criteria in Solid Tumours (RECIST) guideline V1.1 (specifically, no ascites, pleural or pericardial effusions, osteoblastic bone metastases, or carcinomatous lymphangitis of the lung as the only lesion). For GBM patients: Measurable disease as defined by RANO criteria.
• Adequate bone marrow function defined as:
• absolute neutrophil count ≥ 1.5 x 109/L (being \> 2 weeks off hematopoietic growth factors),

You may not qualify if:

• Major surgery, chemotherapy, radical radiotherapy, investigational agents, or other anticancer therapy in the last 4 weeks before treatment start.
• For all patients with the exception of GBM patients: active central nervous system (CNS) metastases, as indicated by clinical symptoms, cerebral edema, and/or progressive growth (subjects with a history of CNS metastases or cord compression are allowable if they have been definitively treated and have been clinically stable for at least 3 months, and off steroids or anticonvulsants, before day 1 treatment).
• For GBM patients: disease progression within three months following last prior radiation therapy.
• Inability or unwillingness to swallow.
• Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the IMP (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, or malabsorption syndrome)
• Any other cancer within 3 years prior to enrolment, with the exception of adequately treated carcinoma in situ of the cervix uteri, or adequately treated basal or squamous cell carcinoma of the skin.
• Significant liver disease, including active viral, alcoholic or other hepatitis and cirrhosis.
• History of HIV infection, active hepatitis B (chronic or acute), or hepatitis C infection. Patients with past or resolved hepatitis B infection (defined as having a negative HBsAg test and positivity for antibodies for hepatitis B core antigen \[anti-HBc\]) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is negative for HCV RNA
• Severe infections within 4 weeks prior to enrolment.
• Patients with a history of central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and precluding informed consent or adversely affecting compliance with study drug.
• Baseline left ventricular ejection fraction (LVEF) \< 50% by echocardiography or multi-gated scintigraphic scan (MUGA)
• Other current severe, uncontrolled systemic disease
• Treatment with CYP3A4/5 inhibitors within 5 drug elimination half-lives before study treatment start and/or inability or unwillingness to avoid such medications during study treatment
• Known hypersensitivity to any study drug components
• Pregnant or lactating women

Sponsors & Collaborators

• Phost'In Therapeutics: lead

Study Sites (4)

Institut du Cancer de Montpellier

Montpellier, 34298, France

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

RECRUITING

IRCCS Ospedale San Raffaele

Milan, 20132, Italy

RECRUITING

Azienda Unità Sanitaria Locale - IRCCS di Reggio Emilia

Reggio Emilia, 42123, Italy

RECRUITING

MeSH Terms

Conditions

Neoplasms; Glioblastoma; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Alain Herrera, MD

  Phost'In Therapeutics

  STUDY DIRECTOR

• Diego Tosi, MD

  Institut du Cancer de Montpellier - Val d'Aurelle

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karine Chorro, Mrs.

CONTACT

+33 (0) 4 11 93 77 51; phast@phostin.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: First-in-human clinical trial, including 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.

Study Record Dates

• First Submitted: July 27, 2022
• First Posted: August 10, 2022
• Study Start: July 18, 2022
• Primary Completion: November 4, 2024
• Study Completion (Estimated): July 31, 2027
• Last Updated: April 8, 2025

Record last verified: 2025-04

Locations

IT (3); FR (1)