Clinical trial NCT06841185: A Study to Compare the Efficacy, Safety, Immunogenicity, and Pharmacokinetic Profile of HLX13 with YERVOY As a First-Line Treatment for Patients with Unresectable Hepatocellular Carcinoma
Official title: A Randomized, Multicenter, Double-Blind, Parallel-Controlled Integrated Phase I/III Clinical Study to Evaluate the Efficacy, Safety, Immunogenicity, and Pharmacokinetic Profile of Ipilimumab Biosimilar HLX13 Vs. YERVOY® (US-Sourced YERVOY® and EU-Sourced YERVOY®) As a First-Line Treatment for Patients with Unresectable Hepatocellular Carcinoma
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE3
Conditions: Hepatocellular Carcinoma (HCC)
Keywords: Ipilimumab Biosimilar
Lead sponsor: Shanghai Henlius Biotech
Sponsor class: INDUSTRY
First posted: 2025-02-24
Enrollment: 656
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a multicenter, randomized, double-blind, parallel-controlled integrated phase I/III clinical study to evaluate the efficacy, safety, PK, and immunogenicity of HLX13 and YERVOY® in patients with unresectable hepatocellular carcinoma who have not received prior systemic therapy.

Detailed description: This study includes three treatment groups. Patients will be randomly assigned at a 2:1:1 ratio to the HLX13, US-sourced YERVOY®, or EU-sourced YERVOY® group to receive the treatment of IMPs in combination with nivolumab.

Patients with good tolerability and disease control will receive HLX13 or YERVOY® in combination with nivolumab on the first day of every 3 weeks for up to 4 cycles. PK and immunogenicity blood sampling will be conducted during the treatment period. After the four treatment cycles, all subjects will be subsequently treated with nivolumab monotherapy until investigator-assessed disease progression, initiation of a new anti-neoplastic therapy, withdrawal of informed consent, death, unacceptable toxicity, or up to 1 year after randomization, whichever occurs first.

Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically diagnosed relapsed metastatic or advanced hepatocellular carcinoma not eligible for surgical or locoregional therapies according to the diagnostic criteria of the American Association for the Study of Liver Diseases (AASLD).
* At least one measurable lesion as assessed by IRRC based on RECIST v1.1 within 4 weeks prior to the first dose in this study.
* No systemic therapy for relapsed metastatic or advanced hepatocellular carcinoma prior to screening.
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
* Child-Pugh Class A.
* Normal major organ functions.
* Women of childbearing potential should use highly effective methods of contraception during the study and within 5 months after the last study treatment; Male subjects capable of fathering a child must agree to use at least one highly effective method of contraception for the duration of the study and for at least 7 months after the last study treatment.

Exclusion Criteria:

* With other histopathological types of hepatocellular carcinoma.
* History of hepatic encephalopathy.
* Clinically significant ascites.
* Patients with tumor thrombus at the main portal vein, left or right portal (either or both) vein branch, or inferior vena cava.
* Presence of the central nervous system disorders at screening, except subjects who have previously received treatment for brain metastases can participate in the study treatment if their clinical symptoms have been stable for at least 4 weeks.
* Evidence of portal hypertension with bleeding esophageal or gastric varices within 6 months prior to the randomization.
* Known active or suspected autoimmune diseases.
* Active co-infection with both hepatitis B and C, or hepatitis D infection in subjects with hepatitis B.
* Uncontrolled cardiovascular diseases within 6 months.
* Known interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, and severe lung function abnormalities that may impede the investigators' diagnosis and management of drug-related pulmonary toxicity prior to screening.
* Patients who have received any T-cell costimulatory agents or immune checkpoint blockade therapy, including but not limited to cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors, PD-1 inhibitors, PD-L1/2 inhibitors, or other agents that target T cells.
* Patients who have other conditions not suitable for inclusion per investigator's judgments.

Primary outcomes:
measure: Area under the serum concentration-time curve from time 0 to 21 days (AUC0-21d)
timeFrame: Up to Day 21
measure: Area under the serum concentration-time curve within a dosing interval at steady-state (AUCss)
timeFrame: Up to Day 85
measure: Best Objective Response Rate (ORR) up to Week 24 (assessed by Independent Radiology Review Committee [IRRC] based on RECIST v1.1)
timeFrame: Up to Week 24
Secondary outcomes:
measure: Maximum serum drug concentration (Cmax) after the first dose
timeFrame: Up to Day 21
measure: Trough serum drug concentration (Ctrough) after the first dose
timeFrame: Up to Day 21
measure: Time to reach maximum serum drug concentration (Tmax) after the first dose
timeFrame: Up to Day 21
measure: Elimination half-life (t1/2) after the first dose
timeFrame: Up to Day 21
measure: Total clearance (CL) after the first dose
timeFrame: Up to Day 21
measure: Volume of distribution during terminal phase (Vz) after the first dose
timeFrame: Up to Day 21
measure: Time to reach maximum serum drug concentration at steady state (Tmax, ss)
timeFrame: Up to Day 85
measure: Maximum serum drug concentration at steady state (Cmax, ss)
timeFrame: Up to Day 85
measure: Minimum serum drug concentration at steady state (Cmin, ss)
timeFrame: Up to Day 85
measure: Elimination half-life (t1/2) at steady state
timeFrame: Up to Day 85
measure: Volume of distribution at steady state (Vss)
timeFrame: Up to Day 85
measure: Total clearance at steady state (CLss)
timeFrame: Up to Day 85
measure: Accumulation ratio of AUC (Rac, AUC)
timeFrame: Up to Day 85
measure: Accumulation ratio of Cmax (Rac, Cmax)
timeFrame: Up to Day 85
measure: ORR assessed by IRRC (based on RECIST v1.1)
timeFrame: Up to Week 30
measure: ORR assessed by investigators (based on RECIST v1.1)
timeFrame: Up to Week 48
measure: Duration of Response (DOR) assessed by investigators (based on RECIST v1.1)
timeFrame: Up to Week 48
measure: Time to Response (TTR) assessed by investigators (based on RECIST v1.1)
timeFrame: Up to Week 48
measure: Progression-Free Survival (PFS) Status assessed by investigators (based on RECIST v1.1)
timeFrame: Up to Week 48
measure: Progression-Free Survival Rate (PFSR) assessed by investigators (based on RECIST v1.1) at Weeks 24 and 48
timeFrame: Up to Week 48
measure: Overall Survival (OS)
timeFrame: Up to 1 year
measure: Overall Survival Rate (OSR) assessed by investigators (based on RECIST v1.1) at Weeks 24 and 48
timeFrame: Up to Week 48
measure: Adverse events (AEs)
timeFrame: Up to Month 15
measure: Serious adverse events (SAEs)
timeFrame: Up to Month 15
measure: Incidence of anti-drug antibodies (ADAs).
timeFrame: Up to 1 year
measure: Incidence of neutralizing antibodies (NAbs).
timeFrame: Up to 1 year
Other outcomes:
Locations:
Study officials:
References: