Solid tumor
Conditions
Interventions
Dose escalation group:The dose escalation of HRS-6208 will be based on an accelerated titration design combined with a BOIN design. The patients with advanced solid tumors were enrolled with sequentia
Sponsors
West China Hospital of Sichuan University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Patients with unresectable locally advanced or metastatic solid tumors confirmed by histology or cytology, who have relapsed or progressed after standard treatment, or have no standard treatment options, or are not suitable for standard treatment at this stage; 2. Age 18-75 years old (including both ends); 3. ECOG score 0-1; 4. Estimated survival time >=12 weeks; 5. At least one measurable tumor lesion according to RECIST v1.1 (dose-escalation subjects are allowed to have only non-target lesions); 6. There is sufficient bone marrow and organ function, and the following test results should be completed within 7 days before the first study treatment: a) Routine blood examination (no blood transfusion or hematopoietic stimulating factor treatment within 14 days before the examination) : neutrophil count (ANC) >=1.5× 109 /L (1,500/mm3), platelets >=100× 109 /L (100,000/mm3), hemoglobin (Hgb) >=9.0 g/dL (90g/L); b) Liver function test: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =60 mL/min (using Cockcroft-Gault formula); d) Coagulation function test: prothrombin time and partial thromboplastin time <=1.5×ULN; 7. A fertile woman must consent to contraception, use acceptable contraceptive methods with her partner from the time of signing the informed consent until 1 month before the last medication, and must have a negative serum HCG test within 7 days before the first medication, and must be non-lactating; 8. Male patients whose partner is a fertile woman must consent to contraception, use a condom within one month from the start of the experimental drug treatment until the last dose, and use acceptable contraceptive methods with their partner. Male patients must also agree not to donate sperm within the same time frame. Male subjects with a pregnant partner are required to use condoms and do not need to use other methods of contraception. 9. Subjects are required to give informed consent to this study before the experiment and sign a written informed consent voluntarily. Therapeutic extension stage HR positive, HER2-negative breast cancer 1. Confirmed HR-positive and HER2-negative breast cancer according to the latest tumor biopsy sample: a) HR positive is defined as estrogen receptor (ER) and/or progesterone receptor (PR) positive when immunohistochemical staining shows that no less than 1% of tumor nuclei show varying degrees of staining; b) HER2-negative criteria: immunohistochemical staining intensity of 0 or 1+; If the strength is 2+, in situ hybridization must be performed to confirm negative; 2. Recurrence and metastasis stage During or after endocrine therapy, recurrence and progression of the disease confirmed by clinical or imaging; 3. Has been treated with CDK4/6 inhibitors (adjuvant phase and/or relapsing and metastatic phase); 4. The stage of recurrence and metastasis can be treated with chemotherapy or antibody drug conjugate. Pancreatic ductal adenocarcinoma 1. Pancreatic ductal adenocarcinoma confirmed histologically or cytologically; 2. The previous treatment regimen included at least one or more of gemcitabine, platinum and fluoropyrimidine cytotoxic drugs; 3. Prior treatment with immune checkpoint inhibitors is permitted; 4. No biliary obstruction, seve
Exclusion criteria
Exclusion criteria: 1. History of other malignancies within the past 5 years, excluding cured basal cell carcinoma of the skin and carcinoma in situ of the cervix; 2. The adverse reactions of previous anti-tumor therapy have not returned to the level defined by NCI-CTCAE v5.0 rating 450 ms (male) or QTcF>470ms (female) obtained by 12-lead electrocardiogram at rest; 3) Acute coronary syndrome, congestive heart failure (NYHA heart function grade =II), aortic dissection, stroke, or other grade 3 or above cardiovascular and cerebrovascular events occurred within 6 months before the first administration of the drug; 4) Left ventricular ejection fraction (LVEF) 180 mmHg and/or diastolic blood pressure > 100 mmHg after medication); 6. The first study of arteriovenous thrombosis events occurring within 6 months before medication, such as cerebrovascular accidents, deep vein thrombosis and pulmonary embolism; 7. Severe infection, including but not limited to bacteremia requiring hospitalization and severe pneumonia, occurs within 4 weeks prior to the first medication; Active infection of grade CTCAE>=2 requiring systemic antibiotic treatment within 2 weeks prior to the first dose; 8. Clinically significant bleeding symptoms occurred within 3 months before the first study; 9. The subject has a history of active autoimmune disease, immune deficiency and autoimmune disease, or a history of disease or syndrome requiring systemic steroid hormone or immunosuppressive drug treatment, or other acquired (HIV infection), congenital immunodeficiency disease, or a history of organ transplantation (including allogeneic bone marrow transplantation); 10. Untreated active hepatitis (active hepatitis B, defined as hepatitis B surface antigen [HBsAg] positive with HBV-DNA higher than 500IU/ml; Active hepatitis C, defined as HCV-RNA above the minimum detectable limit); 11. Patients with active pulmonary tuberculosis infection within 1 year before enrollment were found through medical history or CT examination, or had a history of active pulmonary tubercu
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| DLT;RP2D;Laboratory indicators;MTD;12-lead ECG;ECOG score;Physical examination;Vital signs;Adverse events (AEs and SAEs); | — |
Secondary
| Measure | Time frame |
|---|---|
| Cmax;Bioavailability in a relatively fasting state after a meal;Objective Response Rate, ORR;Tmax;AUC0-t;AUC0-8;t1/2;Vz/F;CL/F;Cmax,ss;Tmax,ss;Cmin,ss;AUCss;Rac;Duration of Response, DoR;Disease Control Rate,DCR;Progression Free Survival, PFS;Overall Survival,OS; | — |
Countries
China
Contacts
Public ContactPing Feng / Ting Luo
West China Hospital of Sichuan University
Outcome results
None listed