Hepatocellular Carcinoma
Conditions
Keywords
MRG006A, Pucotenlimab, Bevacizumab, TKI
Brief summary
This is an open-label, multicenter, Phase I/II clinical study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of MRG006A in combination with immune checkpoint inhibitors and targeted therapy in patients with advanced hepatocellular carcinoma (HCC).
Interventions
Sponsors
Lepu Biopharma Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Able to understand and provide written informed consent, and comply with the requirements specified in the protocol. 2. Life expectancy ≥ 3 months. 3. Must provide tumor tissue specimens for GPC3 testing. 4. Histologically/cytologically confirmed hepatocellular carcinoma (HCC), Barcelona Clinic Liver Cancer (BCLC) Stage C or Stage B not amenable to curative surgery and/or locoregional therapy. 5. At least one measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) and modified RECIST (mRECIST). 6. No prior systemic antineoplastic therapy for unresectable HCC before first dose administration. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, with no deterioration within 2 weeks prior to first study drug administration. 8. Adequate organ function as specified. 9. Negative serum pregnancy test within 7 days prior to first dose (women of childbearing potential). Pregnant or lactating women are not eligible for this study. 10. Women of childbearing potential and male patients must agree to use adequate contraception during MRG006A treatment and for 180 days after the last infusion.
Exclusion criteria
1. Prior histologically/cytologically confirmed diagnosis of hepatocellular carcinoma with fibrolamellar, sarcomatoid, cholangiocarcinoma, or other components. 2. History of hepatic failure or hepatic encephalopathy, or history of liver transplantation. 3. Pleural effusion, ascites, or pelvic effusion, or clinically significant pericardial effusion. 4. Acute or chronic active hepatitis B or hepatitis C infection. 5. Central nervous system metastases. 6. Prior locoregional therapy for hepatocellular carcinoma within 4 weeks before first dose administration. 7. Receipt of live attenuated vaccines within 4 weeks before first dose or planned administration during the study period. 8. Major surgical procedure within 4 weeks before first dose, or the presence of unhealed wounds, ulcers, or bone fractures. 9. Uncontrolled or poorly controlled medical conditions. 10. Toxicities from prior therapy that have not resolved to Grade 0 or 1 before first dose of study treatment. 11. Severe cardiac insufficiency or cerebrovascular events within 6 months prior, or occurrence of pulmonary embolism, deep vein thrombosis, gastrointestinal perforation and/or fistula, or intestinal obstruction. 12. Patients with double or multiple primary malignancies. 13. Hypersensitivity to any component or excipient of the investigational product. 14. Active or poorly controlled severe infection. 15. Any severe and/or uncontrolled systemic disease that, in the opinion of the investigator and sponsor, renders the patient unsuitable for participation in this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | Up to 2 years | Proportion of participants experiencing treatment-related adverse events as assessed by CTCAE v5.0 |
| Recommended Phase 2 Dose | 1 year | Evaluate RP2D based on the safety and efficacy of different dosage cohorts. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak concentration (Cmax) | Up to 2 years | Cmax of ADC, TAb, free payload will be measured. |
| Time to peak (Tmax) | Up to 2 years | Tmax of ADC, TAb, free payload will be measured. |
| Area under the concentration versus time curve (AUC) | Up to 2 years | AUC of ADC, TAb, free payload will be measured. |
| Half-life time (t1/2) | Up to 2 years | t1/2 of ADC, TAb, free payload will be measured. |
| Anti-Drug Antibody characteristics | Up to 2 years | Proportion of subjects who develop treatment-emergent anti-drug antibody (ADA) positivity. |
| Objective Response Rate | 6 months | Proportion of patients with complete response/partial response assessed by Response Criteria in Solid Tumor version 1.1 |
| Disease Control Rate | 6 months | Proportion of patients with complete response/partial response and stable disease assessed by Response Criteria in Solid Tumor version 1.1 |
| Duration of Response | Up to 2 years | The time from the first documentation of objective tumor response (CR or PR) until disease progression or death from any cause |
| Progression-Free Survival | Up to 2 years | Time between the start of study treatment and progressive disease or any cause of death |
Countries
China
Contacts
CONTACTProgram Director
Outcome results
None listed