Hepatocellular Carcinoma (HCC)
Conditions
Keywords
Ipilimumab Biosimilar
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.
Interventions
DRUGHLX13
HLX13 (3 mg/kg) and nivolumab (1 mg/kg) treatment on the first day of each cycle, every 3 weeks with a total of 4 cycles
DRUGUS-sourced YERVOY®
US-sourced YERVOY® (3 mg/kg) and nivolumab (1 mg/kg) treatment on the first day of each cycle, every 3 weeks with a total of 4 cycles
DRUGEU-sourced YERVOY®
EU-sourced YERVOY® (3 mg/kg) and nivolumab (1 mg/kg) treatment on the first day of each cycle, every 3 weeks with a total of 4 cycles
Sponsors
Shanghai Henlius Biotech
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area under the serum concentration-time curve from time 0 to 21 days (AUC0-21d) | Up to Day 21 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Area under the serum concentration-time curve within a dosing interval at steady-state (AUCss) | Up to Day 85 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Best Objective Response Rate (ORR) up to Week 24 (assessed by Independent Radiology Review Committee [IRRC] based on RECIST v1.1) | Up to Week 24 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Elimination half-life (t1/2) after the first dose | Up to Day 21 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Total clearance (CL) after the first dose | Up to Day 21 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Volume of distribution during terminal phase (Vz) after the first dose | Up to Day 21 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Time to reach maximum serum drug concentration at steady state (Tmax, ss) | Up to Day 85 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Maximum serum drug concentration at steady state (Cmax, ss) | Up to Day 85 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Minimum serum drug concentration at steady state (Cmin, ss) | Up to Day 85 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Elimination half-life (t1/2) at steady state | Up to Day 85 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Volume of distribution at steady state (Vss) | Up to Day 85 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Total clearance at steady state (CLss) | Up to Day 85 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Accumulation ratio of AUC (Rac, AUC) | Up to Day 85 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Accumulation ratio of Cmax (Rac, Cmax) | Up to Day 85 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Maximum serum drug concentration (Cmax) after the first dose | Up to Day 21 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| ORR assessed by investigators (based on RECIST v1.1) | Up to Week 48 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Duration of Response (DOR) assessed by investigators (based on RECIST v1.1) | Up to Week 48 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Time to Response (TTR) assessed by investigators (based on RECIST v1.1) | Up to Week 48 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Progression-Free Survival (PFS) Status assessed by investigators (based on RECIST v1.1) | Up to Week 48 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Progression-Free Survival Rate (PFSR) assessed by investigators (based on RECIST v1.1) at Weeks 24 and 48 | Up to Week 48 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Overall Survival (OS) | Up to 1 year | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Overall Survival Rate (OSR) assessed by investigators (based on RECIST v1.1) at Weeks 24 and 48 | Up to Week 48 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Adverse events (AEs) | Up to Month 15 | — |
| Serious adverse events (SAEs) | Up to Month 15 | — |
| Incidence of anti-drug antibodies (ADAs). | Up to 1 year | — |
| Incidence of neutralizing antibodies (NAbs). | Up to 1 year | — |
| ORR assessed by IRRC (based on RECIST v1.1) | Up to Week 30 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Trough serum drug concentration (Ctrough) after the first dose | Up to Day 21 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
| Time to reach maximum serum drug concentration (Tmax) after the first dose | Up to Day 21 | Detailed Outcome Measure will be defined in the Statistical Analysis Plan |
Outcome results
None listed