Unresectable Locally Advanced or Metastatic Solid Tumors
Conditions
Interventions
Dose escalation phase group:SYHA1815 tablets
Dose expansion phase group:SYHA1815 tablets
Sponsors
Jilin Provincial Tumor Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. The age at the time of obtaining the informed consent is 18-75 years (including the cut-off value), regardless of gender; 2. Histological or cytological confirmation of unresectable locally advanced or metastatic solid tumors (thyroid cancer, non-small cell lung cancer, gastric cancer [including gastroesophageal junction cancer], colorectal cancer, pancreatic cancer, soft tissue sarcoma, etc.), according to standards Treatment failure (disease progression or intolerance), or no standard treatment to choose from or rejection of standard treatment; 3. The time between the end of the last anti-tumor treatment and the first administration of SYHA1815 meets the following time intervals: cytotoxic drugs, PD-1/PD-L1, cellular immunotherapy >= 4 weeks; oral molecular targeted drug therapy, etc. >= 2 weeks; radiotherapy End time >= 4 weeks (palliative local radiotherapy for pain relief >= 2 weeks), and has recovered from the meaningful effects of radiotherapy; anti-cancer Chinese medicine or Chinese patent medicine >= 2 weeks; 4. ECOG physical performance (PS) score 0-1; 5. Estimated survival time >= 12 weeks; 6. There is at least one measurable lesion that meets the definition of RECIST v1.1 during the baseline period; 7. The organ function level and related laboratory indicators of the subject within 7 days before the first administration must meet the following requirements (not receiving blood transfusion treatment 14 days before the first administration): (1) The absolute value of neutrophil count (ANC) >= 1.5x10^9/L; platelet count >= 75x10^9/L; hemoglobin .= 90g/L; and blood phosphorus and calcium are within the normal range; (2) Blood biochemistry: serum total bilirubin <= 1.5 times the upper limit of normal (ULN); AST/ALT <= 3 times ULN (if there is liver metastasis, allow AST/ALT <= 5 times ULN); serum creatinine <= 1.5 times ULN; (3) Coagulation: International normalized ratio (INR) or prothrombin time (PT) <= 1.5ULN, activated partial thrombin time (APTT) <= 1.5ULN; 8. The result of serum pregnancy test within 7 days before the first administration of fertile women must be negative, and female subjects are willing to take adequate contraceptive measures during the test period and at least 3 months after the last administration of the study drug. Male subjects must agree to take contraceptive measures (non-drug or tool contraception) from the beginning of the study to at least 3 months after the last medication. 9. Volunteer to participate in the research and sign the informed consent form.
Exclusion criteria
Exclusion criteria: 1.The previous anti-tumor or surgical treatment history with any of the following conditions: (1)Received the treatment of other intervention clinical studies with 4 weeks before the first dose of study drug; (2)Had undergone major surgery within 4 weeks before the first dose of study drug or had not fully recovered from any previous invasive operation; (3)Prior treatment of RET/FGFR inhibitors or small molecular kinase inhibitors with RET/FGFR as the main targets; 2.Any unresolved toxicities from prior anti-tumor therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1, except for alopecia, pigmentation, previous chemotherapy-related neurotoxicity (= grade III), and unstable angina pectoris within 6 months prior to screening;Cerebrovascular disease occurred within 6 months before screening (except for transient ischemic attack (TIA), lacunar infarction with no clinical significance);Severe uncontrollable arrhythmia requiring medical treatment;Electrocardiogram (ECG) examination, female QTc interval > 470 milliseconds (ms), male QTc interval>450 milliseconds (ms) according to Fridericia formula;The left ventricular ejection fraction is less than 50% according to cardiac ultrasound examination; 5.History of active bleeding within 6 months before screening; 6.Any serious or uncontrollable disease, and not suitable for this study as determined by the investigator; 7.Any uncontrollable active infection that will prevent the subjects from receiving the study drug within 2 weeks prior to the first dose of study drug; 8.HIV positive, HCV positive with HCV RNA quantity higher than the upper limit of normal value in the research center; 9.Active hepatitis B infection, with the HBV DNA quantity higher than the upper limit of normal value of the research center; 10.A history of any other malignant tumors within 5 years (except for effectively controlled non-melanoma skin basal cell carcinoma, cervical carcinoma in situ, and other malignant tumors that have been effectively controlled without treatment in the past 5 years; 11.Subjects who have taken potent inhibitors and inducers of CYP3A4 liver metabolic enzymes within 2 weeks before the first administration and still need to continue to use such drugs; 12.Women who are breastfeeding; 13.Concomitant disease or condition that may interfere with the conduct of the trial, or that would pose an unacceptable risk to the subject in this trial in the opinion of the Investigator.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with Dose-limiting Toxicities;Incidence of adverse events and SAEs;Safety laboratory examination, vital signs, ECG, physical examination, etc; | — |
Secondary
| Measure | Time frame |
|---|---|
| PK indicators;Curative effect index;Biomarkers and beneficiaries; the relationship between RET ? FGFR gene changes and efficacy.; | — |
Countries
China
Contacts
Public ContactCheng Ying
Jilin Provincial Tumor Hospital
Outcome results
None listed