The purpose of this study is to evaluate the impact of iparomlimab and tuvonralimab as preoperative neoadjuvant therapy on recurrence-free survival (RFS), along with its potential improvement in overall survival (OS), in patients with resectable hepatocellular carcinoma (HCC) at high risk of recurrence.
CCGLC-017 is a prospective, open-label, single-arm, exploratory clinical study. This study primarily evaluates the impact of iparomlimab and tuvonralimab (QL1706) as preoperative neoadjuvant therapy on recurrence-free survival (RFS), with exploratory analysis of its potential benefits on overall survival (OS) in patients with resectable hepatocellular carcinoma (HCC) at high risk of recurrence. Enrolled patients will receive a single dose of iparomlimab and tuvonralimab within one week prior to surgery, followed by six cycles of iparomlimab and tuvonralimab therapy postoperatively.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
26
Neoadjuvant phase: A single cycle of Iparomlimab and Tuvonralimab (7.5 mg/kg) will be administered within 1 week prior to surgery. Adjuvant phase: Six cycles of Iparomlimab and Tuvonralimab (7.5 mg/kg, Q3W) will be initiated starting at 2 weeks postoperatively.
Will be performed at an appropriate interval following neoadjuvant therapy initiation.
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Wuhan, Hubei, China
Recurrence-Free Survival (RFS)
The duration will be calculated from the date of achieving complete response (CR) after surgery to the first documented occurrence of intrahepatic or extrahepatic HCC recurrence, or death from any cause, whichever comes first.
Time frame: From the date of achieving complete response (CR) after surgery until the date of first documented recurrence or death from any cause, assessed up to 24 months post-surgery.
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.
Time frame: from the date of first treatment to the date of death from any cause, assessed up to 5 years
Major Pathological Response (MPR)
Defined as the presence of ≤50% residual viable tumor cells in the resected specimen confirmed by postoperative pathological examination.
Time frame: Intraoperative frozen section assessment and final postoperative pathology (assessed within 4 weeks after surgery).
Investigator-Assessed Recurrence-Free Survival (RFS)
Defined as the time from treatment initiation to the first documented intrahepatic or extrahepatic HCC recurrence, or death from any cause (whichever occurs first), as determined by the investigator.
Time frame: From treatment initiation until the date of first documented HCC recurrence or death from any cause, whichever occurs first, assessed up to 24 months.
Time to Recurrence (TTR)
Defined as the time from treatment initiation to the first documented intrahepatic or extrahepatic HCC recurrence event.
Time frame: From treatment initiation until the date of first documented HCC recurrence, assessed up to 24 months.
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IRF-Assessed RFS Rate at 12 and 24 Months
Defined as the proportion of patients without documented intrahepatic/extrahepatic HCC recurrence or death from any cause at 12 and 24 months post-treatment, assessed by an independent review facility (IRF) using standardized imaging criteria (RECIST 1.1/mRECIST).
Time frame: At 12 and 24 months post-treatment.
Investigator-Assessed RFS Rate at 12 and 24 Months
Defined as the proportion of patients without documented intrahepatic/extrahepatic HCC recurrence or death from any cause at 12 and 24 months post-treatment, as assessed by the investigator.
Time frame: At 12 and 24 months post-treatment
OS Rate at 12 and 24 Months
Defined as the proportion of patients surviving at 12 and 24 months post-treatment initiation.
Time frame: At 12 and 24 months post-treatment initiation.
Time to Extrahepatic Spread (EHS) or Macrovascular Invasion
Defined as the time from treatment initiation to the first radiologically or histologically confirmed occurrence of either extrahepatic metastasis or macrovascular invasion (portal/hepatic vein involvement).
Time frame: From treatment initiation until the date of first documented EHS or macrovascular invasion, assessed up to 24 months.
RFS in PD-L1-High Subgroup or macrovascular invasion (portal/hepatic vein involvement).
Defined as recurrence-free survival in patients with PD-L1-high expression (predefined as combined positive score \[CPS\] ≥1 by immunohistochemistry) assessed by both investigator and IRF.
Time frame: From the date of achieving complete response (CR) after surgery until the date of first documented HCC recurrence or death from any cause, whichever comes first, assessed up to 24 months post-surgery.
Incidence of Adverse Events (AEs)
Defined as the proportion of participants experiencing adverse events, graded per Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Time frame: From the first dose of iparomlimab/tuvonralimab administration until 90 days after the last dose of adjuvant therapy (up to approximately 34 weeks).