Study of GNS561 in Patients With Liver Cancer

NCT03316222 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: GNS561-CL-I-Q-0211
• Study Type: interventional
• Target: 50
• Locations: 3 countries
• Sites: 5

Brief Summary

This is a first in human, open-label dose escalation study to investigate the safety, tolerability and pharmacokinetics of GNS561 in patients Primary and Secondary liver cancer

Conditions

Hepatocellular Carcinoma; Cholangiocarcinoma, Intrahepatic

Outcome Measures

Primary Outcomes (1)

• Dose-Limiting Toxicity

  Dose-Limiting Toxicity will be measured by adverse events by dose level

  Dose-Limiting Toxicity will be evaluated during the 4 - week dose escalation phase.

Study Arms (2)

Dose escalation

EXPERIMENTAL

Dose escalation using 3+3 design with dose limiting toxicity (DLT) observation period of 28 days.

Drug: GNS561

Dose Expansion

EXPERIMENTAL

Additional patients will be enrolled into the recommended dose. These additional patients will undergo all of the same assessments as the patients enrolled in dose escalation with the exception of PK sampling.

Drug: GNS561

Interventions

GNS561 DRUG

Escalating doses to be administered 3 times a week.

Dose Expansion; Dose escalation

Eligibility Criteria

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

You may qualify if:

• Males or females ≥ 18 years of age
• Histologically confirmed and documented locally advanced or metastatic HCC that is deemed not appropriate for curative therapy and Histologically confirmed and documented locally advanced or metastatic iCCA.
• Liver tumor burden\< 50% of the liver (per Investigator judgment)
• Antiviral therapy required in hepatitis B virus patients (Hepatitis B antigen positive)
• Willing to have liver biopsy at the beginning of cycle 2 (Day 1)
• Presence of a measurable tumor per RECIST v1.1 criteria
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
• Life expectancy ≥ 12 weeks
• Adequate hematologic function prior to the first dose of GNS561, defined as:
• Absolute neutrophils count ≥ 1500 cells/µL
• Hemoglobin ≥ 10 g/dL with no transfusion within 4 weeks prior to first planned dose of GNS561
• Platelet count \> 50,000/µL with no transfusion within 2 weeks prior to first planned dose of GNS561
• Adequate renal function prior to first dose, defined as
• Serum creatinine \< 1.5 ULN
• Creatinine clearance ≥ 50 mL/min/m2 (by Cockroft-Gault equation of 24-hour urine) if creatinine ≥ 1.5 X ULN

You may not qualify if:

• Pregnant or breast-feeding mothers
• Any known history of encephalopathy
• Known esophageal varices with recent history of bleeding (within previous 2 months)
• Clinically significant ascites or paracentesis
• Known untreated or symptomatic brain metastases
• Presence of residual toxicities of ≥ Grade 2 after prior antitumor therapy ≤ 4 weeks prior to first dose. Grade 1 toxicities related to previous treatments are acceptable at the time of the first planned dose of GNS561, as well as any alopecia.
• Chronic treatment with immunosuppressive agents (like steroids) ≤ 6 weeks prior to first planned dose of GNS561.
• Major surgical procedures, open biopsy or significant traumatic injury ≤ 4 weeks prior to first dose of GNS561 or anticipation of major surgical procedure during the course of the trial, minor surgical procedures ≤ 1 week of first planned dose
• Any clinically significant cardiovascular condition as judged by the Investigator
• Severe or uncontrolled renal condition
• Untreated chronic hepatitis B
• Known history of immunodeficiency diseases (e.g., active HIV)
• Use of any prohibited concomitant medications within 14 days of the Baseline/Day 1 visit
• Known current alcohol (\> 20g/ Day in women and \> 30g/ Day in men) or substance abuse
• Malabsorption issues (e.g., gastric bypass or gastrectomy patients)

Sponsors & Collaborators

• Genoscience Pharma: lead

Study Sites (5)

Memorial Sloan Kettering

New York, New York, 10065, United States

Location

Jules Bordet Institute

Brussels, Belgium

Location

CHU Grenoble

Grenoble, 38043, France

Location

Croix-Rousse Hospital

Lyon, 69004, France

Location

Saint-Joseph Hospital

Paris, 75014, France

Location

Related Publications (1)

• Harding JJ, Awada A, Roth G, Decaens T, Merle P, Kotecki N, Dreyer C, Ansaldi C, Rachid M, Mezouar S, Menut A, Bestion EN, Paradis V, Halfon P, Abou-Alfa GK, Raymond E. First-In-Human Effects of PPT1 Inhibition Using the Oral Treatment with GNS561/Ezurpimtrostat in Patients with Primary and Secondary Liver Cancers. Liver Cancer. 2022 Feb 15;11(3):268-277. doi: 10.1159/000522418. eCollection 2022 Jun.

  PMID: 35949290 DERIVED

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Cholangiocarcinoma

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2017
• First Posted: October 20, 2017
• Study Start: April 4, 2018
• Primary Completion: January 15, 2021
• Study Completion: April 25, 2022
• Last Updated: May 2, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1); BE (1); FR (3)