A Phase Ib/II Trial Evaluating the Efficacy and Safety of Adebrelimab, Camrelizumab Plus Apatinib as First-line Therapy in Patients With Advanced Hepatocellular Carcinoma
Overview
- Phase
- Phase 1
- Intervention
- adebrelimab, camrelizumab plus apatinib
- Conditions
- Advanced Hepatocellular Carcinoma
- Sponsor
- Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
- Enrollment
- 52
- Locations
- 1
- Primary Endpoint
- Objective Response Rate
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a prospective, single-arm, phase Ib/II trial . The objective of this study is to evaluate the efficacy and safety of adebrelimab, camrelizumab plus apatinib as first-line therapy in patients with advanced hepatocellular carcinoma
Detailed Description
This study is divided into two stages: in the Ib stage, the tolerance and safety of adebrelimab, camrelizumab plus apatinib in the treatment of patients with advanced solid tumors were studied; The second phase is a single-arm, open and multi-center clinical study. The improvement of objective response rate (ORR) in patients with advanced HCC by first-line treatment with adebrelimab, camrelizumab plus apatinib was observed and evaluated. ■ The first stage In order to effectively investigate the safety of adebrelimab, camrelizumab plus apatinib in the treatment of patients with advanced solid tumors, the following cohort (dose level) studies are planned: Queue 1: adebrelimab 10mg/kgQ3W+ camrelizumab 200mgQ3W+ apatinib 250mgqd. Queue 2: adebrelimab 20mg/kgQ3W+ camrelizumab 200mgQ3W+ apatinib 250mgqd. Using i3+3 design, 3\~6 subjects are expected to be enrolled in each cohort. Every 3 weeks (21 days) is a treatment cycle, and DLT observation period is the first and second cycles of combined administration. After passing the safety evaluation of DLT observation period, the next dose group experiment can be gradually entered. ■ The second stage According to the results of the first phase, the recommended dose of phase II study (RP2D) was selected for further efficacy and safety evaluation in patients with advanced hepatocellular carcinoma who had not received systematic treatment before. The objective remission rate (ORR) was the main end point of the study, and 46 subjects were planned to be enrolled. After fully knowing and signing the informed consent form, the subjects will receive the study treatment: adebrelimab (RP2D, Q3W)+ camrelizumab 200mgQ3W+ apatinib 250mgqd, with 3 weeks (21 days) as a treatment cycle.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients volunteered to join this study and signed informed consent;
- •≥ 18 years old (calculated on the day of signing the informed consent), both men and women can be used;
- •Patients with advanced or metastatic solid tumor confirmed by histology or cytology (stage Ⅰb); Patients with hepatocellular carcinoma diagnosed by EASL/AASLD diagnostic criteria, histopathology or cytology are not suitable for surgery or local treatment, or progress after surgery and/or local treatment (stage II);
- •Subjects must be able to provide fresh or archived tumor tissues (formalin-fixed, paraffin-embedded \[FFPE\] tissue blocks or at least 5 unstained FFPE slides) and their pathological reports. If the subjects can provide less than 5 unstained slides or the tumor tissue is unavailable (for example, because of previous diagnostic tests), after discussion, they may be allowed to join the group according to the specific circumstances;
- •For patients who have progressed after local treatment, local treatment (including but not limited to surgery, radiotherapy, hepatic artery embolization, TACE, hepatic artery perfusion, radiofrequency ablation, cryoablation or percutaneous ethanol injection) has been completed at least 4 weeks before the baseline imaging scan, and the toxic reactions caused by local treatment (except alopecia) must be restored to the fifth edition of the National Cancer Institute-General Terminology Standard for Adverse Events (NCI-CTCAEV
- •rating ≤1 level;
- •Never received any systematic treatment for HCC before;
- •There is at least one measurable lesion (according to the requirements of RECISTv1.1, the long diameter of the measurable lesion in spiral CT scanning is ≥10mm or the short diameter of swollen lymph nodes is ≥ 15 mm; Lesions that have received local treatment in the past can be used as target lesions after definite progress according to RECISTv1.1 standard);
- •Child-Pugh liver function classification: A or B)
- •The score of physical condition of the Eastern Cancer Cooperative Group (ECOG) is 0 \~ 2;
Exclusion Criteria
- •Cholangiocarcinoma, sarcomatoid HCC, mixed cell carcinoma and fibreboard cell carcinoma; Have other active malignant tumors except HCC within 5 years or at the same time. Localized tumors that have been cured, such as basal cell carcinoma of skin, squamous cell carcinoma of skin, superficial bladder cancer, prostate cancer in situ, cervical cancer in situ, breast cancer in situ, etc., can be included in the group;
- •Patients who are ready to undergo or have previously received an organ or allogeneic bone marrow transplantation;
- •Received other experimental drugs within 28 days before starting the study treatment;
- •Moderate and severe ascites with clinical symptoms requires therapeutic puncture, drainage or Child-Pugh score \> 2 (except for those who only show a small amount of ascites on imaging but are not accompanied by clinical symptoms); Uncontrolled or moderate or above pleural effusion and pericardial effusion;
- •Patients who have a history of gastrointestinal bleeding or have a clear tendency of gastrointestinal bleeding within 6 months before the start of the study and treatment, such as: bleeding-risk or severe esophageal and gastric varices, local active gastrointestinal ulcer lesions, and persistent fecal occult blood positive, can not be included in the group (if the fecal occult blood is positive in the baseline period, it can be rechecked, if it is still positive after the recheck, it needs to undergo gastroduodenoscopy (EGD), and if the EGD indicates bleeding-risk esophageal and gastric varices, it can not be included).
- •Abdominal fistula, gastrointestinal perforation or abdominal abscess occurred within 6 months before the start of the study treatment;
- •Known hereditary or acquired bleeding (such as coagulation dysfunction) or thrombotic tendency, such as hemophilia patients; At present, or in the near future (within 10 days before the start of the study treatment), full-dose oral or injection anticoagulants or thrombolytic drugs have been used for therapeutic purposes (low-dose aspirin and low-molecular-weight heparin are allowed for preventive use);
- •Aspirin (\> 325mg/ day (maximum antiplatelet dose) or dipyridamole, ticlopidine, clopidogrel and cilostazol are currently being used or recently used (within 10 days before the start of the study treatment);
- •Thrombosis or embolism occurred within 6 months before the start of the study, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction) and pulmonary embolism;
- •There are clinical symptoms or diseases of the heart that are not well controlled, such as: (1) Cardiac insufficiency above Grade II according to the standards of new york Heart Association (NYHA) or cardiac color Doppler examination: LVEF (Left Ventricular Ejection Fraction) \< 50%; (2) Unstable angina pectoris; (3) myocardial infarction occurred within one year before the start of study and treatment; (4) Clinically significant supraventricular or ventricular arrhythmia needs treatment or intervention; (5) QTc \> 450 ms (male); QTc\>470ms (female) (QTc interval is calculated by Fridericia formula; If the QTc is abnormal, it can be continuously detected for three times every 2 minutes, and the average value can be taken);
Arms & Interventions
Interventional arm
Intervention: adebrelimab, camrelizumab plus apatinib
Outcomes
Primary Outcomes
Objective Response Rate
Time Frame: Up to approximately 2 years
The proportion of subjects who achieved complete response (CR; the disappearance of any intratumoural arterial enhancement in all target lesions) or partial response (PR; at least a 30% decrease in the sum of the longest viable tumour diameters of target lesions) according to the mRECIST standard.
Adverse events (AEs) and serious adverse events (SAEs)
Time Frame: Up to approximately 2 years
The incidence and severity of adverse events (AEs) and serious adverse events (SAEs) of adebrelimab, camrelizumab plus apatinib as first-line therapy in patients with advanced hepatocellular carcinoma.
Secondary Outcomes
- Progression Free Survival(Up to approximately 2 years)
- Duration of Response(Up to approximately 2 years)
- Time to Progression(Up to approximately 2 years)
- Overall Survival(Up to approximately 2 years)
- Disease Control Rate(Up to approximately 2 years)