Hepatocellular Carcinoma
Conditions
Brief summary
This is a multi-center, double-blind, randomized, phase III study to investigate the efficacy and safety of Nofazinlimab (CS1003) in combination with lenvatinib and placebo in combination with lenvatinib in the treatment of subjects with no prior systemic treatment and with unresectable advanced hepatocellular carcinoma (HCC). Subjects cannot be eligible for locoregional therapy. In this study, Nofazinlimab (CS1003) (or placebo) and lenvatinib are both considered as the study treatment while Nofazinlimab (CS1003) (or placebo) is the investigational product and lenvatinib is selected as the basic treatment for HCC.
Interventions
DRUGNofazinlimab (CS1003)+Lenvatinib
Nofazinlimab (CS1003), intravenous (i.v.) administration every 21 days; Lenvatinib oral administration, once daily
DRUGNofazinlimab (CS1003) Placebo+Lenvatinib
Nofazinlimab (CS1003) Placebo, i.v. administration every 21 days ; Lenvatinib oral administration, once daily
Sponsors
CStone Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 years on the day of signing informed consent-(For Taiwan, the lower limit of age is 20 years). 2. Subjects with unresectable advanced HCC, that is not eligible for surgery and/or locoregional therapy (Stage B or C based on Barcelona Clinic Liver Cancer \[BCLC\] staging system, and meets either one of the following criteria: 1) histologically or cytologically confirmed diagnosis of HCC, 2) clinically confirmed diagnosis of HCC according to American Association for the Study of Liver Diseases (AASLD) criteria. Patients without cirrhosis require histological confirmation of diagnosis. 3. With at least one measurable lesion can be assessed 4. Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1. 5. Life expectancy ≥ 3 months. 6. Child-Pugh A 7. No prior systemic treatment for advanced HCC 8. Subjects with hepatitis B virus (HBV) infection, are willing to continue receiving antiviral treatment while on study. 9. Subjects have adequate organ and marrow function. Female subjects with childbearing potential must have negative serum pregnancy test result at screening. Female subjects with childbearing potential, and male subjects and their female partners with childbearing potential must agree to use an contraceptive method(s) from the day of signing informed consent form (ICF), during the study and till at least 6 months after the last dose of study treatment.
Exclusion criteria
10. Fibrolamellar-HCC, sarcomatoid, cholangiocellular carcinoma or mixed cholangiocarcinoma and HCC. 11. A prior bleeding event due to esophageal within 6 months or other gastrointestinal bleeding events within 28 days prior to screening. 12. Malabsorption syndrome or inability to take oral medication due to other causes. 13. HBV and HCV co-infection. 14. Investigator evaluates to increase the drug related risk caused by enrolling subjects in trial and taking study drug, or any serious or uncontrolled systematic disease that confound the drug absorption or the study outcome, e,g diabetes mellitus, hypertension, rheumatoid arthritis, major cardiovascular disease and so on. 15. Surgery or locoregional therapy for palliative purpose within 4 weeks prior to study treatment. 16. History of other malignancy(ies) in the past 5 years, except for malignant disease treated with curative intent and without active disease. 17. Known history of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS). 18. Current or prior use of systemic corticosteroid (\> 10 mg/day prednisone or equivalent) or other immunosuppressive medication within 14 days prior to the first dose of study treatment. 19. History of bone marrow transplantation or organ transplantation. 20. History of anaphylaxis or hypersensitivity to any ingredient of the investigational product. 21. Any contraindication of lenvatinib. 22. Known history of drugs abuse that would interfere with cooperation with the requirements of the trial. 23. Pregnant or lactating female subjects. 24. History of psychiatric disease that would interfere with cooperation with the requirements of the trial; lack of or with restricted physical capability. 25. QTc interval \> 470 msec (as calculated with Fridericia's formula) at screening electrocardiogram (ECG); 26. Any condition that would in the investigator's judgment, prevent the subject from participating in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From enrollment to end of follow-up, a median of 42.5 months | OS was defined as the time interval between the date of randomization to the date of death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Assessed by Blinded Independent Central Review Committee(BICR) | From enrollment to end of follow-up, a median of 42.5 months | ORR assessed by BICR was defined as the proportion of participants who achieve objective response (complete response \[CR\] or partial response \[PR\]) assessed by BICR based on RECIST v1.1. |
| Progression-free Survival(PFS) Assessed by Blinded Independent Central Review Committee(BICR) Based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 | From enrollment to end of follow-up, a median of 42.5 months | PFS assessed by BICR was defined as the time from the date of randomization to disease progression assessed by BICR or death, whichever occurs first. |
| Progression-free Survival(PFS) Evaluated by Investigator Based on RECIST v1.1 | From enrollment to end of follow-up, a median of 42.5 months | — |
| Objective Response Rate (ORR) Evaluated by Investigators Based on RECIST v1.1 | From enrollment to end of follow-up, a median of 42.5 months | — |
| Duration of Response (DoR) Evaluated by Blinded Independent Central Review Committee(BICR) Based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 | From enrollment to end of follow-up, a median of 42.5 months | — |
| Duration of Response (DoR) Evaluated by Investigators Based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 | From enrollment to end of follow-up, a median of 42.5 months | — |
| Disease Control Rate (DCR) Evaluated by Blinded Independent Central Review Committee(BICR) Based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 | From enrollment to end of follow-up, a median of 42.5 months | — |
| Disease Control Rate (DCR) Evaluated by Investigators Based on Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 | From enrollment to end of follow-up, a median of 42.5 months | — |
| Percentage of Participants With Adverse Events | From enrollment to end of follow-up, a median of 42.5 months | — |
| Peak and Trough Serum Concentrations of CS1003 | Peak: assessed post-dose (within 30 minutes after the end of infusion) on Cycle 4 Day 1; Trough: assessed pre-dose (within 60 minutes prior to infusion) on Cycle 4 Day 1 (cycle length = 21 days). | — |
| Number and Percentage of Subjects Who Develop Anti-CS1003 Antibody (ADA) | From enrollment to end of follow-up, a median of 42.5 months | — |
| Time to Deterioration (TTD), Defined as the Time From Randomization to the First Deterioration of European Organization for the Research and Treatment of Cancer (EORTC) Quality-of-Life Questionnaire Core 30 (QLQ-C30) Scale | From enrollment to end of follow-up, a median of 42.5 months | — |
Countries
China, Italy, Poland, Spain, Taiwan, United States
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 143 Participants |
| Age, Categorical Between 18 and 65 years | 391 Participants |
| Age, Continuous | 57.1 years STANDARD_DEVIATION 11.23 |
| Eastern Cooperative Oncology Group Performance Status ECOG = 0 | 148 Participants |
| Eastern Cooperative Oncology Group Performance Status ECOG = 1 | 205 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 534 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 509 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 15 Participants |
| Region of Enrollment China | 488 participants |
| Region of Enrollment Poland | 6 participants |
| Region of Enrollment Spain | 16 participants |
| Region of Enrollment Taiwan | 16 participants |
| Sex: Female, Male Female | 29 Participants |
| Sex: Female, Male Male | 303 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 253 / 352 | 137 / 181 |
| other Total, other adverse events | 343 / 352 | 180 / 181 |
| serious Total, serious adverse events | 138 / 352 | 55 / 181 |
Outcome results
None listed