Advanced Hepatocellular Carcinoma (HCC)
Conditions
Brief summary
This is a randomized, open-label, international, multi-center, phase III trial to evaluate the efficacy and safety of Camrelizumab Combined with Rivoceranib Mesylate versus Investigator's Choice of Regimen in Treatment of Patients with Hepatocellular Carcinoma (HCC)
Interventions
DRUGcamrelizumab；Rivoceranib
Camrelizumab at 200 mg via intravenous administration (IV), once every 2 weeks (Q2W), in combination with 250 mg of rivoceranib mesylate, oral administration, once a day (QD)
DRUGRivoceranib
Rivoceranib mesylate (750 mg, QD, po)
DRUGSorafenib
Sorafenib tosylate (400 mg, twice a day (BID), po)
DRUGRegorafenib
Regorafenib (160 mg, administer for 21 days then stop for 7 days, po)
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized，Open，Controlled, International Multi-Center
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject must participate voluntarily and sign the informed consent form; 2. Aged ≥ 18 years old, male or female; 3. Histopathologically confirmed hepatocellular carcinoma; 4. Has PD on treatment with prior anti-PD-1/PD-L1/CTLA-4 monoclonal antibody (mAb) administered either as monotherapy or as combination therapy. 5. No more than 2 lines of previous system treatment; 6. Be able to provide fresh or archived tumor tissue samples; 7. Patient with at least one measurable lesion (for Stage I); 8. Barcelona clinic liver cancer: Stage B or C; 9. Child-Pugh score: ≤ 7; 10. ECOG PS score of 0-1; 11. Life expectancy of ≥ 12 weeks; 12. Adequate organ function 13. Must take one medically approved contraceptive measure
Exclusion criteria
1. Patients with any active, known or suspected autoimmune disorder; 2. Patients who have used corticosteroids or other immunosuppressive agents for systemic treatment within 1 month prior to randomization; 3. With known severe allergic reactions to any other monoclonal antibodies; 4. Received previous camrelizumab or rivoceranib mesylate treatment; 5. Patients who discontinued ICIs treatment due to immune-related toxicity; 6. Patients with known CNS metastasis or hepatic encephalopathy; 7. Patients with liver tumor burden greater than 50% of total liver in volume, or patients who have previously undergone liver transplantation;; 8. Patients with symptomatic ascites or pleural effusion requiring paracentesis and drainage, or patients who have undergone ascites or pleural effusion drainage within 2 weeks before randomization; 9. Patients with other malignancies currently or within the past 5 years; 10. Patients with hypertension which cannot be well controlled by antihypertensives; history of hypertensive crisis or hypertensive encephalopathy; 11. Uncontrolled cardiac diseases or symptoms； 12. Known hereditary or acquired bleeding disorders; 13. Clinically significant bleeding symptoms or clear bleeding tendency; 14. Patients with gastrointestinal perforation or gastrointestinal fistula; 15. Patients with significant vascular invasions with a high possibility of fatal bleeding; 16. Patients with important arterial/venous thrombosis; 17. Patients experiencing toxicity caused by previous anti-tumor therapy that has not recovered to Grade ≤ 1; 18. Patients with active infection; 19. Patients with congenital or acquired immune deficiency; 20. Patients who received live vaccines within 28 days prior to randomization, or are expect to be vaccinated during the treatment period; 21. Patients with other potential factors that may affect the study results.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Stage I：Objective Response Rate（ORR） | 2.5 years |
| Stage II：Overall survival （OS） | 2.5 years |
Secondary
| Measure | Time frame |
|---|---|
| Adverse Events（AEs） | 2.5 years |
| Stage II：Objective Response Rate（ORR） | 2.5 years |
| Disease Control Rate（DCR） | 2.5 years |
| Duration of Response（DoR） | 2.5 years |
| Proportion of neutralizing antibody (Nab) | 2.5 years |
| time to progression （TTP） | 2.5 years |
| Pharmacokinetics (PK) Ctrough of camrelizumab | 2.5 years |
| Pharmacokinetics (PK) Ctrough of Apatinib | 2.5 years |
| Proportion of anti- camrelizumab antibody (ADA) | 2.5 years |
| Progression-Free-Survival （PFS） | 2.5 years |
| Stage I：Overall survival （OS） | 2.5 years |
Countries
China
Outcome results
None listed