GT90001 Plus Nivolumab in Patients With Advanced Hepatocellular Carcinoma

Hepatocellular Carcinoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05178043
• Other study ID #: GT90001-MR-1001
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: August 1, 2021
• Est. completion date: December 1, 2025

Study information

• Verified date: February 2024
• Source: Suzhou Kintor Pharmaceutical Inc,
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 5
• Est. completion date: December 1, 2025
• Est. primary completion date: April 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Hepatocellular
• HCC
• Hepatocellular Carcinoma

Intervention

Drug:
• Nivolumab
Nivolumab 240mg to be administered as an intravenous (IV) infusion every 2 weeks (Q2W).
• GT90001
GT90001 7mg/kg to be administered as an intravenous infusion every 2 weeks (Q2W) after Nivolumab infusion.

Locations

Country	Name	City	State
United States	City of Hope National Medical Center	Duarte	California
United States	Renovatio Clinical	Houston	Texas
United States	Los Angeles Hematology Oncology Medical Group	Los Angeles	California
United States	NYU Langone Health	New York	New York
United States	Medical Oncology Associates	Spokane	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Suzhou Kintor Pharmaceutical Inc,

Country where clinical trial is conducted

United States, 

Outcome

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