Donafenib tosylate tablets are sorafenib , regorafenib similar drugs , inhibit tumor anti-angiogenesis; inhibit tumor growth, and regulate tumor blood vessel microcirculation.
Terreplimumab (Tuoyi) is a anti-PD-1 receptor fully human monoclonal antibody , which can block T lymphocytes ’s PD-1 , Blocking its binding to PD-L1 on the surface of tumor cells, relieves the immunosuppression of tumor cells on immune cells, allowing immune cells to regain anti-tumor cell immunity and kill tumor cells.
Hepatic Artery Chemoembolization (TACE) refers to a treatment method that uses minimally invasive intervention to inject chemotherapeutic drugs and embolic drugs into the hepatic artery through a catheter to kill tumor cells. For liver cancer cells, most of the blood supply comes from hepatic artery . Therefore, choosing to inject drugs into the hepatic artery supplying liver cancer can not only obtain high concentration of drugs in the tumor, but also block the tumor blood supply, which has a dual role in the treatment of liver cancer. TACE is also known as interventional therapy , interventional therapy , is currently recognized as one of the most commonly used non-surgical methods for the treatment of liver cancer .
study drug: sorafenib tosylate Dona sheet (I s) test type
: cantilever test
Test title: Donafenib tosylate tablets, treprilimab injection (JS001) combined with TACE in patients with inoperable liver cancer Dose escalation study of
Indications: advanced hepatocellular carcinoma (first line) _p9 _p9 p1198 h
_p9 p7 Years (including cutoffs),male or female.
2. Patients with unresectable hepatocellular carcinoma diagnosed in accordance with the "Guidelines for the Diagnosis and Treatment of Primary Liver Cancer" (Ministry of Health 2019 Edition) or through histopathology and/or cytology .
3. There is at least one measurable lesion (according to RECIST v1.1).
4. Patients with hepatocellular carcinoma confirmed by the investigator as feasible for TACE treatment, the largest tumor diameter (cm) + number (pieces) ≥ 6, the largest tumor diameter ≤ 10 cm and the largest number of nodules ≤ 10, The total tumor volume accounts for less than 50% of the liver;
5. Child-Pugh score of liver function is Grade A.
6. ECOG 0-1 points.
7. Expected survival period ≥ 12 months.
8. The laboratory test values within 7 days before the first study treatment meet the following criteria: (No blood components, cell growth factor, albumin and others are allowed within 14 days before the test Corrective treatment drugs). a) Routine blood examination: Hb≥90g/L; ANC≥1.5×109/L; PLT≥75×109/L. b) Biochemical examination: Biochemical examination: ALB≥30g/L; ALT and AST≤5×ULN; TBIL≤2×ULN; electrolytes are basically normal or normal after treatment.c) Renal function: serum creatinine ≤1.5×ULN or creatinine clearance (Ccr) ≥50mL/min (Gockcroft-Gault formula). Urine routine: urinary protein <2+.> coagulation function : International standard ratio (INR) or prothrombin time (PT)≤1.5×ULN; activated partial coagulation time (aPTT)≤1.5×ULN.
Exclusion criteria
1. Patients with diffuse liver cancer.
2, uncontrollable hepatic encephalopathy , refractory ascites or hepatorenal syndrome.
3. Patients with intrahepatic cholangiocarcinoma (ICC), HCC-ICC mixed, fibrous lamellar HCC or sarcomatoid HCC.
4, Invasion of large blood vessels , main portal vein tumor thrombosis (except Vp1, Vp2).
5. Those with extrahepatic spread.
6. Spontaneous tumor rupture.
7. Have received systemic anti-tumor therapy in the past,Including chemotherapy, anti-angiogenesis therapy (sorafenib, regorafenib, lenvatinib, apatinib , etc.), other targeted drug therapy or immunotherapy.
8. Target lesions who have previously received TACE or TAE treatment or other local treatments for HCC (Persons who have previously performed local treatment for non-target lesions for ≥ 4 weeks are allowed to be included).
9, HBV-DNA≥104copies/ml (2000IU/ml). If HBV-DNA ≥ 104copies/ml, then perform antiviral treatment first until HBV-DNA drops below 104copies/ml before entering the study, and continue to take antiviral drugs and monitor liver function and hepatitis B virus markers.
10. There is any of the following conditions: a) HIV antibody positive; b) HBV infection combined with HCV infection, by PCR detection of HCV-RNA negative can be regarded as not infected with HCV virus .
11. Those who are known or suspected to be severely allergic to iodine; or have a suspected history of allergy to Donafenib toluenesulfonate tablets or similar drugs; to chimeric or humanized antibodies or fusion proteins A history of severe allergies, allergies, or other hypersensitivity reactions.
12, known to be against biological drugs produced by Chinese hamster ovary cells, or citric acid monohydrate, sodium citrate dihydrate, mannitol , polysorbate (a group of research drugs) Points) People with allergies.
13, with known hematological malignancies, malignant primary brain tumors or malignant sarcomas, other malignant primary solid tumors within 5 years,Unless the patient has received possible curative treatment and there is no evidence of the disease within 5 years. Note: This time requirement (ie within 5 years) does not apply to skin basal cell carcinoma , superficial bladder cancer, skin squamous cell carcinoma, cervical cancer in situ or other patients with carcinoma in situ who have successfully undergone resection;
14. The investigator believes that there is portal hypertension and has a high risk of bleeding; or gastroscopy with red signs.
15, with a history of autoimmune disease (such as autoimmune hepatitis, interstitial pneumonia, 1, vasculitis, , uveitis, ) , nephritis, hyperthyroidism or hypothyroidism, asthma that requires bronchodilator therapy, etc.); patients suffering from vitiligo or asthma in childhood has been completely relieved, and patients who do not need any intervention after adulthood can be included.
16, with active upper gastrointestinal ulcer, obvious vomiting, chronic diarrhea, intestinal obstruction, malabsorption or other diseases known to affect drug absorption, distribution, metabolism or clearance Patients with uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage (once a month or more frequently).
17. Patients who have previously received allogeneic stem cell or solid organ transplantation.
18. Any live vaccine vaccinated within 4 weeks before the first study treatment; used within 4 weeks before the start of the study treatment or within 5 half-life of the drug (whichever is longer) Systemic immunostimulatory agents (including but not limited to interferon and IL-2).
19. Did not fully recover from the previous surgery, and had a medium or large-scale surgery within 4 weeks before the first study medication (except biopsy or intravenous catheter).
20. Patients who have taken Chinese patent medicines with anti-tumor indications or modern Chinese medicine preparations within 2 weeks before the first study treatment.
21. There are any significant clinical or laboratory abnormalities that the investigator believes will affect the safety evaluator, such as: uncontrollable active infection (CTCAEv5.0> 2) (or the first study to treat TACE In the previous week, patients who were systematically using antibiotics), uncontrollable diabetes (after drug treatment, fasting blood glucose> 8.9mmol/l), suffering from high blood pressure and cannot be reduced to the following range after combined treatment with two drugs Patients (systolic blood pressure <140mmHg,>
22, left ventricular ejection fraction (LVEF) <50%;>450ms, female>470ms.
23. There is gastrointestinal bleeding within 6 months before the treatment of the first study or two consecutive fecal occult blood tests are positive at the time of screening (if both fecal occult blood are positive, the gastroesophageal veins of the stomach fundus are excluded by gastroscopy Severe varicose with high risk of bleeding and refractory unhealed gastric ulcer can be included in the group).
24, are receiving immunosuppressive agents, or systemic or absorbable local hormone therapy to achieve immunosuppressive purposes (dose> 10mg/day, prednisone or other effect hormones), And patients who continued to use the drug within 2 weeks before the first study medication.
25. Patients who need to take drugs that may prolong QTc and/or torsade de pointes (TDP) or drugs that affect drug metabolism (sedatives, etc.) at the same time.
26. Patients with active tuberculosis (TB) are receiving anti-tuberculosis treatment or have received anti-tuberculosis treatment within 1 year before screening.
27, pregnant or lactating female patients, or those who are unwilling to use contraception during the trial; within 7 days before the first study treatment, fertile female subjects must confirm that the serum pregnancy test is negative. Reproductive subjects are willing to use effective contraceptive measures during the use of the study drug and within 180 days after the last dose.
28. Those who have participated in any drug or medical device clinical trial within 1 month before the first study treatment.
29. The investigator believes that they have other acute, severe or chronic medical or psychological diseases and are not suitable for participating in clinical trials.
Research Center
Changsha
Bengbu
Zhengzhou
Beijing
Harbin
is subject to later consultation
[Important Reminder] This public number [Global Good Medicine Information] All article information is for reference only.Specific treatment Please follow the doctor's advice !
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