GT90001 Plus Nivolumab in Patients With Advanced Hepatocellular Carcinoma

A Phase II Study to Evaluate the Efficacy and Safety of GT90001 in Combination With Nivolumab as a Second-line Treatment in Subjects With Advanced Hepatocellular Carcinoma

This is a global phase II, open label study in the subjects with Advanced Hepatocellular Carcinoma (aHCC) who were intolerant or had progressed after or intolerant to first-line Immune Checkpoint Inhibitors (ICI) such as Atezolizumab plus Bevacizumab, or ICI plus Tyrosine Kinase Inhibitor (TKI).

Based on published and first-hand experience with the safety and tolerability of both GT90001 and Nivolumab, the proposed dose is GT90001 7 mg/kg in combination with Nivolumab 240 mg, infusion every two weeks.

This study will enroll a total of 105 subjects to receive combinational therapy of Nivolumab and GT90001.

• Nivolumab 240 mg will first be administered by intravenous infusion over 30 minutes, then 30 minutes later, give intravenous infusion of GT90001 7.0 mg/kg over 60 min, once every two weeks.

Study Overview

• Status: Active, not recruiting
• Conditions: HCC; Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Nivolumab; Drug: GT90001

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope National Medical Center
    • Los Angeles, California, United States, 90017
      • Los Angeles Hematology Oncology Medical Group
  • New York
    • New York, New York, United States, 10016
      • NYU Langone Health
  • Texas
    • Houston, Texas, United States, 77056
      • Renovatio Clinical
  • Washington
    • Spokane, Washington, United States, 99208
      • Medical Oncology Associates

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subjects must have confirmed diagnosis of aHCC (locally advanced or metastatic hepatocellular carcinoma) by radiography, histology and/or cytology, not eligible for surgical and/or locoregional therapies; or progressive disease after surgical and/or locoregional therapies (fibrolamellar, sarcomatoid HCC and mixed hepatocellular / cholangiocarcinoma subtypes are not eligible);
• Have Barcelona Clinic Liver Cancer (BCLC) Stage C disease or BCLC Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy;
• Have documented disease progression after or intolerance to first line treatment of immune checkpoint inhibitors(ICI)
• Child-Pugh score ≤ 6 (Child-Pugh A) score within 7 days of first dose of study drug;
• ECOG performance status: 0-1 within 7 days of first dose of study drug;
• Have a predicted life expectancy of greater than 3 months;
• Adequate hematologic and end-organ function functions of the important organs are confirmed.

Exclusion Criteria:

• Presence of tumor thrombus involving main trunk of portal vein (Vp4), inferior vena cava, cardiac involvement of HCC;
• Subjects with untreated or incompletely treated varices with bleeding or high-risk for bleeding. Has had esophageal or gastric variceal bleeding within the last 6 months;
• History of encephalopathy;
• Has a known history of, or any evidence of central nervous system (CNS) metastases and/or carcinomatous meningitis;
• Had history of a solid organ or hematologic transplant;
• Has received locoregional therapy to liver (TACE, TAE, hepatic arterial infusion [HAI], radiation, radioembolization or ablation) within 4 weeks of start of study treatment.
• Had prior systemic TKI treatment prior to start of study treatment;
• Has received prior immune checkpoint inhibitors within 4 weeks of start of study treatment;
• Has received Nivolumab in the first-line systemic therapy:

• Active co-infection with:

  1. Both hepatitis B and C as evidenced by positive HBV surface antigen or detectable HBV DNA and HCV RNA, OR
  2. Hepatitis D infection in subjects with hepatitis B
• Has an active bacterial or fungal infection requiring systemic therapy within 7 days prior to study drug dosing;
• Has a known history of active tuberculosis (Bacillus Tuberculosis);
• Serious, non-healing or dehiscing wound, active ulcer, or untreated bone fracture;
• Thrombotic or embolic events (except HCC tumor thrombus) within the past 6 months, such as cerebrovascular accident (including transient ischemic attacks), pulmonary embolism; If prior history of deep vein thrombosis (DVT) / (pulmonary embolism (PE), the subject needs to be on stable doses of anticoagulation with low molecular weight heparin or oral anticoagulant for at least two weeks;
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis;
• Subjects with any other serious disease considered by the investigator not in the condition to enter into the trial;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GT90001+Nivolumab	Drug: Nivolumab; Nivolumab 240mg to be administered as an intravenous (IV) infusion every 2 weeks (Q2W).; Other Names: Opdivo, ONO-4538, BMS-936558, MDX1106; Drug: GT90001; GT90001 7mg/kg to be administered as an intravenous infusion every 2 weeks (Q2W) after Nivolumab infusion.; Other Names: PF-03446962

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Objective Response Rate (ORR) (confirmed) as evaluated by an Independent Review Committee (IRC) according to RECIST v1.1	ORR is defined as the proportion of participants with best overall response of confirmed complete response (CR) or partial response (PR). RECIST: Response Evaluation Criteria in Solid Tumors	Approximately 2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival (OS)	Approximately 3 years
Duration OF Response (DOR) as evaluated by an IRC according to RECIST v1.1	Approximately 2 years
Progression Free Survival (PFS) as evaluated by an IRC according to RECIST v1.1	Approximately 2 years
Time To Response (TTR) as evaluated by an IRC according to RECIST v1.1	Approximately 2 years
Time to Progression (TTP) as evaluated by an IRC according to RECIST v1.1	Approximately 2 years
Disease Control Rate (DCR) as evaluated by an IRC according to RECIST v1.1	Approximately 2 years
ORR (confirmed) as evaluated by the investigator according to RECIST v1.1	Approximately 2 years
DOR as evaluated by the investigator according to RECIST v1.1	Approximately 2 years
PFS as evaluated by the investigator according to RECIST v1.1	Approximately 2 years
TTR as evaluated by the investigator according to RECIST v1.1	Approximately 2 years
TTP as evaluated by the investigator according to RECIST v1.1	Approximately 2 years
DCR as evaluated by the investigator according to RECIST v1.1	Approximately 2 years
ORR (confirmed) as evaluated by an IRC according to HCC mRECIST	Approximately 2 years
DOR as evaluated by an IRC according to HCC mRECIST	Approximately 2 years
PFS as evaluated by an IRC according to HCC mRECIST	Approximately 2 years
TTR as evaluated by an IRC according to HCC mRECIST	Approximately 2 years
TTP as evaluated by an IRC according to HCC mRECIST	Approximately 2 years
DCR as evaluated by an IRC according to HCC mRECIST	Approximately 2 years
ORR (confirmed) as evaluated by the investigator according to HCC mRECIST	Approximately 2 years
DOR as evaluated by the investigator according to HCC mRECIST	Approximately 2 years
PFS as evaluated by the investigator according to HCC mRECIST	Approximately 2 years
TTR as evaluated by the investigator according to HCC mRECIST	Approximately 2 years
TTP as evaluated by the investigator according to HCC mRECIST	Approximately 2 years
DCR as evaluated by the investigator according to HCC mRECIST	Approximately 2 years
Safety and tolerability (any Advense Events (AEs), Severe AEs , immune-related AEs (irAEs), treatment-related AEs, abnormal laboratory values, etc.	Approximately 2 years
Presence of Anti-Drug Antibodies (ADAs) to GT90001 and Nivolumab during the study relative to the presence of ADAs at baseline	Approximately 2 years

Collaborators and Investigators

• Sponsor: Suzhou Kintor Pharmaceutical Inc,

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2021
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 25, 2021
• First Submitted That Met QC Criteria: December 17, 2021
• First Posted (Actual): January 5, 2022

Study Record Updates

• Last Update Posted (Estimated): February 22, 2024
• Last Update Submitted That Met QC Criteria: February 20, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Digestive System Neoplasms; Liver Diseases; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab
• Other Study ID Numbers: GT90001-MR-1001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No