A Study of QL1706 in Combination With Bevacizumab and/or Chemotherapy as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma

A Phase II/III, Randomized, Open-label, Multi-center Study to Evaluate the Efficacy and Safety of QL1706 in Combination With Bevacizumab and/or Chemotherapy Versus Sintilimab in Combination With Bevacizumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma

The purpose of this study is to assess the efficacy and safety of QL1706 in combination with bevacizumab and/or chemotherapy versus sintilimab in combination with bevacizumab as first-line treatment in patients with advanced hepatocellular carcinoma.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatocellular Carcinoma
• Intervention / Treatment: Drug: Capecitabine; Drug: QL1706; Drug: Bevacizumab; Drug: Oxaliplatin injection; Drug: Sintilimab

• Study Type: Interventional
• Enrollment (Estimated): 668
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Jian Gao; Phone Number: +8613304321400; Email: jian7.gao@qilu-pharma.com

Study Locations

• China
  • Jiangsu
    • Nanjing, Jiangsu, China, 211199
      • Nanjing Tianyinshan Hospital
      • Contact: Shukui Qin
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Zhongshan Hospital, Fudan University
      • Contact: Jia Fan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Subjects participate voluntarily and sign informed consent.
2. Age ≥ 18 and ≤ 80 years old, male or female.
3. Histological or cytological or clinical diagnosis of HCC
4. Barcelona Clinic Liver Cancer stage C. BCLC stage B, not suitable for radical surgery and/or local treatment.
5. No prior systemic therapy for HCC.
6. Child-Pugh ≤7 , no history of hepatic encephalopathy.

Exclusion Criteria:

1. Histologically or cytologically documented fibrolamellar hepatocellular carcinoma, sarcoma-like hepatocellular carcinoma, cholangiocarcinoma, etc.
2. History of malignancy other than HCC within 5 years prior to the start of study treatment.
3. History of liver transplantation, or planned to receive liver transplantation.
4. Moderate or severe ascites with clinical symptoms that require drainage, uncontrolled or moderate or severe pleural and pericardical effusion.
5. Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
6. Involvement of both the main portal vein and the left and right branches by portal vein tumor thrombus, or of both the main trunk and the superior mesenteric vein concurrently, or of inferior vena cava.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; QL1706 in combination with bevacizumab and chemotherapy	Drug: Capecitabine; 1000 mg/m2 orally twice daily for 14 days continuous dosing followed by a 7-day break of each 21-day cycle; Drug: QL1706; 7.5 mg/kg administered as IV infusion on Day 1 of each 21-day cycle; Drug: Bevacizumab; 15 mg/kg administered as IV infusion on Day 1 of each 21-day cycle; Drug: Oxaliplatin injection; 85 mg/m2 administered as IV infusion on Day 1 of each 21-day cycle
Experimental: Arm 2; QL1706 in combination with bevacizumab	Drug: QL1706; 7.5 mg/kg administered as IV infusion on Day 1 of each 21-day cycle; Drug: Bevacizumab; 15 mg/kg administered as IV infusion on Day 1 of each 21-day cycle
Experimental: Arm 3; QL1706 in combination with chemotherapy	Drug: Capecitabine; 1000 mg/m2 orally twice daily for 14 days continuous dosing followed by a 7-day break of each 21-day cycle; Drug: QL1706; 7.5 mg/kg administered as IV infusion on Day 1 of each 21-day cycle; Drug: Oxaliplatin injection; 85 mg/m2 administered as IV infusion on Day 1 of each 21-day cycle
Active Comparator: Arm 4; Sintilimab in combination with bevacizumab	Drug: Bevacizumab; 15 mg/kg administered as IV infusion on Day 1 of each 21-day cycle; Drug: Sintilimab; 200 mg administered as IV infusion on Day 1 of each 21-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR) (Phase II)	ORR was assessed by investigators per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1).	Up to approximately 4 years
Incidence of Adverse Events (AEs) (Phase II)	An adverse event is any untoward medical occurrence in a subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.	Up to approximately 4 years
Overall Survival (OS) (Phase III)	OS was defined as the time from randomization to death due to any cause.	Up to approximately 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR was assessed by investigators per RECIST 1.1	Up to approximately 4 years
Disease Control Rate (DCR)	DCR was assessed by investigators per RECIST 1.1	Up to approximately 4 years
Duration of Response (DOR)	DOR was assessed by investigators per RECIST 1.1	Up to approximately 4 years
Progression-free Survival (PFS)	PFS was assessed by investigators per RECIST 1.1	Up to approximately 4 years
Time to progression (TTP)	TTP was assessed by investigators per RECIST 1.1	Up to approximately 4 years
Objective Response Rate (ORR)	ORR was assessed by investigators per mRECIST	Up to approximately 4 years
Disease Control Rate (DCR)	DCR was assessed by investigators per mRECIST	Up to approximately 4 years
Duration of Response (DOR)	DOR was assessed by investigators per mRECIST	Up to approximately 4 years
Progression-free Survival (PFS)	PFS was assessed by investigators per mRECIST	Up to approximately 4 years
Time to progression (TTP)	TTP was assessed by investigators per mRECIST	Up to approximately 4 years

Collaborators and Investigators

• Sponsor: Qilu Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Jia Fan, Fudan University; Principal Investigator: Shukui Qin, Nanjing Tianyinshan Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2023
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: July 28, 2023
• First Submitted That Met QC Criteria: July 28, 2023
• First Posted (Actual): August 4, 2023

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: July 28, 2023
• Last Verified: July 1, 2023

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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Capecitabine; Oxaliplatin; Bevacizumab
• Other Study ID Numbers: QL1706-308

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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