Advanced malignant tumor
Conditions
Interventions
Experimental group:SYH2039 tablets
Sponsors
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Age>=18 years old (subject to the day of signing the informed consent form); 2. Histologically or cytologically confirmed advanced malignant tumors, and the enrollment population in each stage of the study meets the following requirements; a. Dose Escalation Phase: Advanced Malignancies (Priority Enrollment for Advanced Solid Tumors with MTAP Deletion); b. Dose expansion phase: including but not limited to MTAP-deficient tumors [non-small cell lung cancer, gastric adenocarcinoma (including gastroesophageal junction adenocarcinoma), esophageal cancer, bladder cancer, pancreatic cancer, mesothelioma and other possible tumor types; 3. Failure of adequate standard therapy or no effective standard therapy (Note: treatment failure includes disease progression or toxicity intolerance during or after treatment, and disease progression or intolerance requires evidence of medical records or imaging data); 4. Participants in the dose expansion phase of enrollment need to have MTAP deletion in tumor tissue confirmed by the central laboratory (central laboratory IHC and/or FISH testing); 5. At least one measurable lesion according to RECIST V1.1 criteria; 6. Eastern Oncology Cooperative (ECOG) Strength Score 0-1; 7. Projected survival of at least 3 months; 8. Adequate organ and bone marrow function with laboratory tests meeting the following criteria (no transfusion or hematopoietic stimulating factor therapy within 14 days): a. Neutrophil count (ANC) >=1.5×10^9/L; b. Platelet count (PLT) >=100×10^9/L; c. Hemoglobin (Hb) >=90 g/L; d. Albumin (ALB) >=30 g/L; creatinine (SCr) =50 ml/min (calculated according to the Cockcroft-Gault formula); f. Total bilirubin (TBIL) <=1.5×ULN, TBIL<=3×ULN in participants with liver metastases or liver cancer; g. alanine aminotransferase (ALT) and aspartate aminotransferase (AST) <=2.5×ULN (participants with liver metastases or liver cancer <=5×ULN); h. Activated partial thromboplastin time (APTT) <=1.5×ULN, International normalized ratio (INR) <=1.5×ULN; 9. Eligible participants of childbearing potential (male and female) must agree to use a reliable method of contraception (hormonal contraceptives, barrier method, or abstinence) with their partner for the duration of the trial and for at least 6 months after the last dose. Female individuals of childbearing potential must have a negative blood pregnancy test within 7 days prior to enrollment; 10. Fully understand this clinical trial and voluntarily sign a written informed consent form.
Exclusion criteria
Exclusion criteria: 1. History of other malignant tumors within 3 years or other active malignancies at the same time (cured localized tumors, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, carcinoma in situ of the prostate, carcinoma in situ of the cervix, carcinoma in situ of the breast, etc., can be enrolled); 2. Those with combined bleeding tendency; Those with active bleeding, hemoptysis, or a history of major bleeding within the past 6 months; Those who have been shown by imaging (CT or MRI) that the tumor has invaded important blood vessels, or it is judged by the investigator that the tumor is very likely to invade important blood vessels during the follow-up study period, causing fatal hemorrhage; 3. Presence of active leptomeningeal lesions or brain metastases that are not well controlled. [Participants with suspected or confirmed brain metastases may be enrolled as long as they are asymptomatic and do not require treatment (such as radiotherapy, surgery, or corticosteroid therapy) to control symptoms of brain metastases.] For participants with brain metastases requiring treatment, who have stable symptoms (no hormone maintenance therapy required, no symptoms of brain metastases) for 2 weeks after treatment, they can be enrolled; 4. There are conditions that seriously affect the absorption, distribution, metabolism and excretion of drugs as judged by the investigator (such as inability to swallow drugs orally, active inflammatory bowel disease, chronic diarrhea with intestinal malabsorption, refractory nausea and vomiting, intestinal obstruction, need for long-term intravenous nutrition therapy, etc.); 5. Prior receipt of MAT2A inhibitors (e.g., AG-270, IDE397, S095033, etc.); 6. The adverse reactions of previous anti-tumor therapy have not recovered to the CTCAE V5.0 grade evaluation <=1 grade (except for toxicity that the investigator judges has no safety risk such as alopecia); 7. Received any anti-tumor therapy (including chemotherapy, targeted therapy, immunotherapy, etc.) within 4 weeks or 5 half-lives (whichever is shorter) prior to the first use of the test drug, or used any Chinese patent medicine with anticancer activity approved by the National Medical Products Administration (NMPA) of the People's Republic of China within 2 weeks prior to the first use of the test drug (regardless of cancer type); 8. Concurrent participation in another clinical trial, unless it is an observational (non-interventional) clinical trial or is in the follow-up period of an interventional trial; 9. Individuals who have undergone major surgery or invasive interventional therapy within 4 weeks prior to the first dose of medication, or who plan to undergo systemic or local tumor resection during the study; 10. Known severe allergic reaction to other components and excipients in the study drug or preparation; 11. Active bacterial, fungal, or viral infection (defined as requiring intravenous antibacterial, antifungal, or antiviral drug therapy) prior to the first dose. Individuals who have no clinical manifestations of active infection prior to the first dose and are given prophylactic infection treatment may be considered for enrollment; 12. Within 2 weeks before the first dose, there is an uncontrollable serous effusion that requires frequent drainage or medical intervention (such as pleural effusion, ascites effusion, pericardial effusion, etc.); 13. History of allogeneic organ transplantation or all
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of Adverse Event(AE);Recommended Pharse 2 Dose(RP2D);Maximum tolerated dose( if avaliable)(MTD);Occurrence of Dose limited toxic(DLT);Occurrence of Serious Adverse Event(SAE); | — |
Secondary
| Measure | Time frame |
|---|---|
| PK parameters of SYH2039 tablets, including but not limited to single administration: Cmax, Tmax, t1/2, Vd/F, CL/F, AUC0-T, AUC0-8, etc. Multiple dosing: t1/2, AUC0-tau, Rac, etc;Objective Response Rate, ORR;PD related indicators include: SDMA, SAM, MTA;Duration of Response, DOR;Disease Control Rate, DCR;Progression-Free Survival, PFS; | — |
Countries
China
Contacts
Public ContactWang bin chao
Guangdong Provincial People's Hospital(Guangdong Academy of Medical Sciences)
Outcome results
None listed