QL1706 As Second-line Treatment in Patients with Advanced Hepatocellular Carcinoma (QL1706)

The Efficacy and Safety of QL1706 As Second-line Treatment in Advanced Hepatocellular Carcinoma Patients Refractory to First-line Therapy: a Single-arm, Phase I Study

This is a phase I trial to assess the safety and preliminary efficacy of QL1706 in Treating Advanced Hepatocellular Carcinoma Patients refractory to prior immunotherapy.

Study Overview

• Status: Not yet recruiting
• Conditions: HCC - Hepatocellular Carcinoma
• Intervention / Treatment: Drug: QL1706

Detailed Description

Immune checkpoint inhibitors (ICIs) have produced encouraging results in patients with hepatocellular carcinoma (HCC). Nonetheless, single-agent ICIs are effective in only 15% to 20% of HCC patients. According to the phase 3 LEAP-002 trial, lenvatinib combined with pembrolizumab provides a limited survival advantage over lenvatinib. In China, local treatments combined with tyrosine kinase inhibitors (TKIs) and anti-PD-1 antibodies have been used as the first-line treatment of advanced HCC. However, due to the heterogeneity of cancer, patient responses to monotherapy or combination therapy vary considerably, and only some patients benefit from such therapy. Hence, there is an unmet need to investigate the appropriate treatment for the rapidly expanding group of patients with advanced HCC who had tumor progression on prior anti-PD-1 therapies. QL1706 (PSB205) is a single bifunctional MabPair (a novel technical platform) product consisting of two engineered monoclonal antibodies (anti-PD-1 IgG4 and anti-CTLA-4 IgG1), with a shorter elimination half-life (t1/2) for CTLA-4. The Single-arm, single-center study aims to evaluate the safety and efficacy of QL1706 in treating advanced HCC refractory to prior PD-1 immune checkpoint inhibitors.

• Study Type: Interventional
• Enrollment (Estimated): 21
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: WanGuang Zhang WanGuang Zhang; Phone Number: 13886195965; Email: wgzhang@tjh.tjmu.edu.cn
• Study Contact Backup: Name: Xiaoping Chen Xiaoping Chen; Phone Number: 02783663400; Email: chenxpchenxp@163.com

Study Locations

• China
  • Hubei
    • Wuhan, Hubei, China, 430000
      • Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
      • Contact: WanGuang Zhang WanGuang Zhang; Phone Number: 13886195965; Email: wgzhang@tjh.tjmu.edu.cn
      • Contact: Xiaoping Chen Xiaoping Chen; Phone Number: 02783663400; Email: chenxpchenxp@163.com

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. 18 years ≤ age ≤ 75 years;
3. Child-Pugh liver function score ≤ 7;
4. ECOG PS 0-1;
5. No serious organic diseases of heart, lung, brain, kidney and other organs;
6. Enhanced MRI examination confirmed advanced hepatocellular carcinoma (CNLC stage II and above, Barcelona stage B and above);
7. Puncture biopsy confirming the pathologic type as hepatocellular carcinoma;
8. Disease progression after receiving first-line therapy(Progressed on/relapsed after at least one prior anti-PD-1 treatment).

Exclusion Criteria:

1. Pregnant and lactating women;
2. Suffering from diseases that affect the absorption, distribution, metabolism or clearance of the study drug (e.g., severe vomiting, chronic diarrhea, intestinal obstruction, absorption disorders, etc.);
3. A history of gastrointestinal bleeding within the previous 4 weeks or a definite predisposition to gastrointestinal bleeding (e.g., known locally active ulcer lesions, fecal occult blood of ++ or more, or gastroscopy if persistent fecal occult blood of +) that has not been treated in a targeted manner, or any other condition that may have caused gastrointestinal bleeding (e.g., severe fundal/esophageal varices) as determined by the investigator;
4. Active infections, including: HIV (HIV1/2 antibody) positive; active hepatitis B (HBsAg positive and abnormal liver function); active hepatitis C (HCV antibody positive or HCV RNA ≥103 copies/ml and abnormal liver function); active tuberculosis; and other uncontrolled active infections (CTCAE V5.0 >2 level);
5. Other significant clinical and laboratory abnormalities that, in the opinion of the investigator, affect the safety evaluation, e.g., uncontrolled diabetes mellitus, immunodeficiency disorders, chronic kidney disease, grade II or higher peripheral neuropathy (CTCAE V5.0), and abnormal thyroid function;
6. Prior use of anti-CTLA-4 antibody drugs.
7. Inability to follow the study protocol to receive treatment or follow up as scheduled.

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: Experimental: QL1706; Drug: QL1706	Drug: QL1706; Drug: QL1706 7.5 mg/kg 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
Median progression-free survival(mPFS)	measured from the date of first treatment to radiographically documented progression according to mRECIST 1.1 or death from any cause (whichever occurs first). Participants alive and without disease progression or lost to follow-up will be censored at the date of their last radiographic assessment.	From randomization to the first occurrence of disease progression or death from any cause, whichever occurs earlier, assessed up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]	Adverse Events	Up to 21 days post-the last treatment
overall response rate (ORR) measured by mRECIST criteria	Complete response (CR): Disappearance of any intra-tumoral arterial enhancement in all target lesions; Partial response (PR): At least a 30% decrease in the sum of diameters of viable (enhancement in the arterial phase) target lesions, taking as reference the baseline sum of the diameters of target lesions; Stable disease (SD): Any cases that do not qualify for either partial response or progressive disease; Progressive disease (PD): An increase of at least 20% in the sum of the diameters of viable (enhancing) target lesions, taking as reference the smallest sum of the diameters of viable (enhancing) target lesions recorded since treatment started. ORR=CR+PR.	rom the date of first treatment to radiographically documented progression according to mRECIST, assessed up to 2 year
Overall survival (OS)	Overall survival (OS): measured from date of first treatment to the date of death from any cause. Participants alive or lost to follow-up will be censored at the date of their last visit.	from the date of first treatment to the date of death from any cause, assessed up to 2 year
Disease control rate (DCR)	Percentage of patients that had a CR, PR, or SD ≥ 6 months per mRECIST	from the date of first treatment to radiographically documented response according to mRECIST, assessed up to 2 year

Collaborators and Investigators

• Sponsor: Wan-Guang Zhang
• Collaborators: Qilu Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): February 1, 2025
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: February 7, 2025
• First Submitted That Met QC Criteria: February 7, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 7, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Immunotherapy; QL1706
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Digestive System Neoplasms; Digestive System Diseases; Liver Diseases; Neoplasms, Glandular and Epithelial; Adenocarcinoma; Liver Neoplasms; Carcinoma; Carcinoma, Hepatocellular
• Other Study ID Numbers: QLMA-HCC-IIT-101

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No