The goal of this investigator-initiated, a single-arm, open-label, pilot study is to investigate the safety, tolerability, and efficacy of Intravenous CD-801 treatment in subjects with advanced hepatocellular carcinoma(HCC).
Condition of disease: advanced hepatocellular carcinoma.
Intervention： CD-801 will be administered intravenously for the treatment of HCC. The dosing regimen is planned for a second dose 14 ± 3 days post-initial treatment, followed by subsequent treatments every 28 ± 7 days, with adjustments made based on patient tolerance and therapeutic response. The trial is structured in two phases: dose escalation and dose expansion.
Dose Escalation Phase:
The study employs a i3+3 design to assess escalating CD-801 dosages: 25 μg, 50 μg, and 100 μg. Post-initial dose, a 14-day DLT observation will evaluate tolerability and safety, guiding dose adjustments or selection of the Recommended Dose (RD) for the expansion phase. Cohorts may include up to 9 participants, adjusted for safety.
Dose Expansion Phase:
The expansion phase will use the safe dosage and regimen from the escalation phase, with treatments starting 14 ± 3 days after the initial dose, then every 28 ± 7 days, adjusted as needed. It ends upon complete response, disease progression, toxicity, withdrawal, loss to follow-up, new oncological treatments, or investigator termination, with a final assessment 14 days post-last dose. The phase plans to enroll about 10 participants to further assess CD-801's safety, tolerability, and antitumor effects using mRECIST.
Drug: CD-801, a drug specifically designed to target liver cancer cells and facilitate the expression of HNF4α.
According to Amendment 1, in these two phases, patients who have received at least 4 cycles of HNF4α srRNA (CD-801 or CD-GA-102) therapy and have a tumor assessment of SD (stable disease) or PD (progressive disease) per mRECIST criteria may, after a comprehensive evaluation by the investigator considering the patient's treatment history and the current safety and efficacy data of HNF4α srRNA, continue HNF4α srRNA at the same dose, or have their dose adjusted, in combination with immunotherapy, targeted therapy, or chemotherapy.
Males or females, aged 18 years or older.
Subjects must have confirmed diagnosis of HCC with any of the following criteria according to the American Association for the Study of Liver Diseases criteria.
Unresectable HCC.
Subjects were not eligible for locoregional or systemic therapies, or had disease progression, or would not benefit after at least one of the conventional therapies.
Inadequate liver function：Albumin (ALB) < 25 g/L, or total bilirubin > 5 × the upper limit of normal (ULN), or aspartate aminotransferase (AST), alkaline phosphatase (ALP), or alanine aminotransferase (ALT) >10 × ULN.
Inadequate renal function defined as creatinine >1.5 × ULN or calculated creatinine clearance < 40 mL/min.
Absolute neutrophil count (ANC) < 1.0×109/L, or Platelets < 30×109/L, or Hemoglobin < 8.5 g/dL.
International Normalized Ratio (INR) > 2.3.
Single group
CD-801
DrugCD-801 will be administered intravenously for the treatment of HCC. The dosing regimen is planned for a second dose 14 ± 3 days post-initial treatment, followed by subsequent treatments every 28 ± 7 days, with adjustments made based on patient tolerance and therapeutic response. According to Amendment 1, patients who have received at least 4 cycles of HNF4α srRNA (CD-801 or CD-GA-102) therapy and have a tumor assessment of SD (stable disease) or PD (progressive disease) per mRECIST criteria may, after a comprehensive evaluation by the investigator considering the patient's treatment history and the current safety and efficacy data of HNF4α srRNA, continue HNF4α srRNA at the same dose, or have their dose adjusted, in combination with immunotherapy, targeted therapy, or chemotherapy.
(Escalation part) To evaluate the tolerability and safety for intravenous CD-801 in subjects with hepatocellular carcinoma (HCC)
Safety and tolerability are assessed based on the incidence of Dose-Limiting Toxicities (DLTs) within 14 days post-initial drug administration, along with the frequency and severity of adverse events (AEs), serious adverse events (SAEs), and events leading to treatment discontinuation throughout the treatment period, all evaluated using the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. According to Amendment 1, the primary endpoint has been amended from assessing the incidence and severity of DLTs, adverse events (AEs), serious adverse events (SAEs), and AEs leading to treatment discontinuation (evaluated per NCI-CTCAE 5.0) with HNF4α srRNA therapy to assessing these outcomes for both HNF4α srRNA monotherapy and combination therapy.
(Expansion part) To assess the objective response rate (ORR) by modified Response Evaluation Criteria in Solid Tumours (mRECIST).
To assess the proportion of subjects who have best overall response of complete response or partial response at the time of data cutoff based on mRECIST. According to Amendment 1, the primary endpoint has been updated from evaluating the ORR per mRECIST with HNF4α srRNA therapy to evaluating the ORR for both monotherapy and combination therapy with HNF4α srRNA per mRECIST.
(Escalation part) To assess the objective response rate (ORR) by mRECIST and RECIST v1.1.
To assess the proportion of subjects who have best overall response of complete response or partial response at the time of data cutoff based on mRECIST and RECIST v1.1. According to Amendment 1, this outcome has been updated from evaluating the ORR per mRECIST with HNF4α srRNA therapy to evaluating the ORR for both monotherapy and combination therapy with HNF4α srRNA per mRECIST and RECIST v1.1.
(Expansion part) To evaluate the tolerability and safety for intravenous CD-801 in subjects with HCC
To assess the frequency and severity of AEs, SAEs, and events leading to treatment discontinuation throughout the treatment period, all evaluated using CTCAE 5.0. According to Amendment 1, this outcome has been amended from assessing the incidence and severity of DLTs, adverse events (AEs), serious adverse events (SAEs), and AEs leading to treatment discontinuation (evaluated per NCI-CTCAE 5.0) with HNF4α srRNA therapy to assessing these outcomes for both HNF4α srRNA monotherapy and combination therapy.
(Expansion part) The objective response rate based on RECIST v1.1
To assess the proportion of subjects who have best overall response of complete response or partial response at the time of data cutoff based on RECIST v1.1 According to Amendment 1, this outcome has been updated from evaluating the ORR per mRECIST with HNF4α srRNA therapy to evaluating the ORR for both monotherapy and combination therapy with HNF4α srRNA per mRECIST.
Duration of response based on mRECIST and RECIST v1.1
To assess the time from the first documentation of complete response or partial response to the date of first documentation of disease progression or death (whichever occurs first) based on mRECIST and RECIST v1.1
Health Related Quality of Life based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).
To evaluate the impact of CD-801 treatment on Health Related Quality of Life for subjects treated using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30).
Health Related Quality of Life based on HCC-specific EORTC QLQ-HCC18 questionnaire.
To evaluate the impact of CD-801 treatment on Health Related Quality of Life for subjects treated using HCC-specific EORTC QLQ-HCC18 questionnaire.
Health Related Quality of Life based on European Quality of Life questionnaire.
To evaluate the impact of CD-801 treatment on Health Related Quality of Life for subjects treated using European Quality of Life questionnaire.
The impact of CD-801 treatment on tumor biomarkers in serum.
To investigate the changes in serum tumor biomarkers among subjects with advanced HCC following CD-801 treatment.
Click on the lead sponsor to view all of their trials.
