advanced solid tumor
Conditions
Interventions
advanced hepatocellular carcinoma:Oral FH-2001 combined with Serplulimab
gastric cancer:Oral FH-2001 combined with Serplulimab
Sponsors
Zhongshan Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily participate in clinical trials and provide written informed consent. 2. Age = 18 years old but =75 years old, male or female. 3. Cohort 1: Histologically and/or cytologically confirmed locally advanced/metastatic hepatocellular carcinoma, failure of or intolerant to at least one standard systematic treatment (disease progression or intolerance, including but not limited to, e.g., chemotherapy, targeted therapy, immunotherapy, antivascular therapy, etc.). Cohort 2: Unresectable histologically and/or cytologically confirmed locally advanced/metastatic gastric adenocarcinoma (including adenocarcinoma of the gastroesophageal junction) and failure of at least one systematic anti-tumor therapy (disease progression or intolerance) , or relapse or progression within 6 months of the last dose of adjuvant/neoadjuvant chemotherapy, which is considered as one line systematic treatment); Previous treatments include, but are not limited to, chemotherapy, targeted therapy, immunotherapy, antivascular therapy, etc. 4. Best response to previous treatments is Previous clinical benefit (PCB) (the criteria for clinical benefit are complete remission of CR, partial remission of PR or disease stable SD maintained for more than 3 months). 5. According to Response Evaluation Criteria in Solid Tumors (RECIST 1.1), there should be at least one measurable lesion (hollow organs such as stomach and esophagus should not be considered as a measurable lesion), and measurable lesions should not have received local treatment such as radiotherapy (the lesion located in the area of previous radiotherapy can also be selected as a target lesion if it is confirmed progression). 6. ECOG status 0-1. 7. Expected survival =3 months. 8. Have adequate organ function as assessed in the laboratory tests: Hematology: Absolute neutrophil count =1.0×109/L Platelet > 75×109/L Hemoglobin > 90g/L or > 5.6 mmol/L, requiring no transfusions of concentrated red blood cells (pRBC) in the past 1 week, may allow stable doses of erythropoietin (=3 months) therapy Renal function: Serum creatinine or Creatinine clearance (CrCl) or glomerular filtration rate (GFR) (Cockcroft-Gault) 60 mL/min(for subjects with creatinine levels = 1.5×ULN) Urine protein Urine protein =1+ or 24-hour urine protein quantity < 1.0g Liver function: Total bilirubin (serum) =1.5×ULN; HCC subjects and subjects with liver metastases, =2.0×ULN, subjects with Gilbert syndrome =3.0×ULN; AST, ALT, ALP =2.5×ULN; HCC subjects and subjects with liver metastases =5×ULN Coagulation function: International Normalized ratio (INR) or prothrombin time (PT) < 1.5×ULN (subjects receiving anticoagulant therapy at a stable dose for nearly two weeks (subjects with HCC are not allowed to take anticoagulants at the same time) 9. Female subject with childbearing potential must have negative serum pregnancy test result at screening(within 7 days before administration). 10. Subjects agree to take effective contraceptive measures from signing of the informed consent till at least 90 days after the last dose of investigational treatment. This includes, but not limited to: abstinence from sex, vasectomy for men, sterilization for women, effective Iuds, and effective contraceptive drugs. Note: Females of non-reproductive age include those who are permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy) and post-menopausal subjects. Females =50 years are considered postmenopausal if they
Exclusion criteria
Exclusion criteria: 1. Received antitumor biologic therapy, antitumor immunotherapy, or other investigational therapies within 4 weeks prior to first dose of study treatment; Received chemotherapy or targeted therapies within 14 days or 5 times of drug half-life prior to first dose of study treatment (whichever is shorter). 2. Recived therapeutic major surgery within 4 weeks prior to first dose of study drug or expected to recieve major surgery during the study period. For subjects who have had drainage (e.g., chest cavity, biliary tract, etc.) and/or had a drainage tube placed within 4 weeks prior to administration, the relevant symptoms/signs should have substantially relieved without usage of prophylactic/therapeutic antibiotic. 3. Received radiotherapy within 4 weeks prior to first dosing (other than palliative radiotherapy for non-target lesions) or abdominal/pelvic radiotherapy within 60 days prior to first dosing. Palliative radiotherapy should be completed at least 48 hours prior to first dosing. Palliative radiotherapy for non-target lesions is permitted. 4. History of gastrointestinal diseases within 3 months prior to first dosing, such as esophageal varicose veins, gastric and duodenal active ulcers, ulcerative colitis, portal hypertension, or active bleeding from unresectosed tumors, or other conditions identified by the investigator as likely to cause gastrointestinal bleeding or perforation; Known inherited or acquired bleeding and thrombotic tendencies (e.g. hemophilia, coagulation disorders, thrombocytopenia, etc.). 5. History of abdominal or tracheoesophageal fistula, perforation of the digestive tract or intraperitoneal abscess, intestinal obstruction, and/or clinical signs and symptoms of gastrointestinal obstruction. 6. Evidence of free gas in the abdominal cavity, which is not caused by peritoneal puncture or recent surgery. 7. Unexpected weight loss =5% within 1 month prior to first dose, even with peripheral or central venous nutritional support. 8. Active central nervous system metastasis meeting the following criteria: a. require local treatment (surgery, radiation, or other) (brain metastases that are asymptomatic or symptomatic but do not require local treatment may be acceptable); b. Taking steroids > 10mg prednisone (or equivalent)/day before enrollment; c. Continuous usage of antiepileptic drugs is required. 9. Uncontrolled hypertension (systolic blood pressure =140mmHg or diastolic blood pressure =90mmHg); History of hypertensive crisis or hypertensive encephalopathy. 10. Uncontrolled pleural effusion, pericardial effusion, or ascites. 11. Uncontrolled tumor-related pain. 12. History of serious cardiovascular disease, including but not limited to the following conditions: a. Serious heart rhythm or conduction abnormalities that require intervention, such as ventricular arrhythmias and degree II-III atrioventricular blocks; b. Acute coronary syndrome, congestive heart failure, stroke, or other grade 3 or higher cardiovascular events occurred within 6 months prior to first dose; c. New York Heart Association (NYHA) heart function Grade =II or left ventricular ejection fraction (LVEF) < 50%; d. any factors that increase the risk of prolonged QTc or arrhythmia, such as heart failure, hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death at age of younger than 40 years in first-degree relatives , usage of any combination drugs known to prolong the QT interval; e. average QTcF
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| first-cycle adverse events, serious adverse events; | — |
Secondary
| Measure | Time frame |
|---|---|
| Objective response rate (ORR); Disease control rate (DCR),;Clinical benefit rate (Clinical benefit rate, CBR; Duration of response (DOR);Progression-free survival (PFS);Other cycle adverse events, serious adverse events;Pharmacokinetic parameters of ? FH-2001 capsule combined with Srulizumab injection after single or multiple oral administration; | — |
Countries
China
Contacts
Public ContactFan Jia
Zhongshan Hospital
Outcome results
None listed