Advanced solid tumor
Conditions
Interventions
Ia: Dose increasing:YZJ-5053 tablets are administered orally QD. Accelerated titration and "i3+3" method were used for dose escalation.
Ib: Dose extension:YZJ-5053 tablets are administered orally QD.
Sponsors
Shanghai East Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1) Male or female subjects are = 18 years of age on the day of signing the informed consent. 2) Histologically or cytologically confirmed advanced or metastatic solid tumors who have failed standard treatment, or are ineligible for the standard treatment, or have no standard treatment, or declined stansard treatment. 3) Subjects must have at least one measurable target lesion in indication expansion phase (Part 2) as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria which has not received radiotherapy (or progressive disease after radiotherapy), or at least one evaluable lesion in dose escalation phase (Part 1) . 4) Subjects with previously confirmed brain metastases were enrolled if they were clinically asymptomatic, in stable condition, and did not require steroid therapy for at least 4 weeks before the initiation of study treatment. 5) Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1; 6) Life expectancy at least 3 months; 7) Adequate hematologic and organ function at screening and within 28 days prior to initiation of study treatment (without receiving any blood transfusion or hematopoietic stimulating factors within 2 weeks prior to screening),as evidenced by: ANC = 1.5 x 10^9/L; Hemoglobin =85 g/L; Platelets = 75 x 10^9/L; AST or ALT = 3 x ULN , or = 5 x ULN if liver cancer or liver metastases are present. Total bilirubin 50 mL/min according to Cockcroft-Gault equation; INR and APTT< 1.5 ULN; 8) A woman of child-bearing potential (WOCBP) must have a negative serum pregnancy test within 72 hours prior to initiation of study treatment (serum pregnancy test is not required for females of nonchild-bearing potential who have undergone surgical sterilization, such as hysterectomy and/or bilateral oophorectomy, or those who have not experienced menses for 12 consecutive months and are judged to be postmenopausal based on factors such as age and castration therapy). 9) Subjects must agree to use adequate contraceptive methods prior to initiation of study treatment, during the study, and for at least 6 months following the last dose of YZJ-5053 tablets, or for at least 4 months following the last dose of pembrolizumab, whichever is later.
Exclusion criteria
Exclusion criteria: 1) Female subjects who are pregnant or breast-feeding. 2) History of malignancy within 3 years prior to screening, with the exception of the cancer under investigation in this study and curatively treated carcinoma in situ of the cervix, non-melanoma skin cancer, localized prostate cancer or any other tumor that has been treated curatively and with no evidence of disease for at least 3 years (for indication expansion phase [Part 2] only). 3) Presence of uncontrolled pleural effusion, pericardial effusion, or ascites that require recurrent drainage procedures (monthly or more frequently). 4) Impaired cardiac function or clinically significant cardiovascular disease. 5) Conditions or diseases that impair gastrointestinal (GI) function which may significantly alter the absorption of YZJ-5053 tables (e.g. ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection). 6) Subjects with active infection requiring intravenous (IV) antibiotics at the time of screening or within 2 weeks prior to initiation of study treatment. 7) Subjects with positive HIV antibody, or positive hepatitis B surface antigen (HBsAg) with HBV DNA =2×10^3 IU/ml (equivalent to 10^4 copies/ml), or positive hepatitis C virus antibody at the time of screening; 8) Have received chemotherapy within 3 weeks, and radiotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy or any other anti-tumor therapy within 4 weeks prior to initiation of study treatment, excluding the following: Within 6 weeks prior to the first use of the study drug, nitrosourea or mitomycin C; Oral administration of fluorouracil, small molecule targeted drugs, and traditional Chinese medicine with anti-tumor indications within 2 weeks prior to the first use of the study drug; Received other unlisted clinical research drugs or treatments within 4 weeks before the first administration; 9) Subject who could not discontinue use of strong inhibitors or strong inducers of CYP3A and CPY2C8 during the study period. 10) Subjects who have received a live vaccine or live attenuated vaccine within 4 weeks prior to initiation of study treatment. 11) Subjects who have previously received A2aR antagonists or A2aR/A2bR antagonists. 12) AEs from previous antitumor therapy have not recovered to baseline or to CTCAE Grade 1 prior to initiation of study treatment, excluding subjects with alopecia (any grade), peripheral sensory neuropathy (Grade = 2), and any other toxicities of no clinical significance (Grade = 2); 13) Subjects with a known history of autoimmune thyroid disease such as diffuse toxic goiter (Graves disease) , acute or subacute thyroiditis. Subjects with active autoimmune diseases or a known history of autoimmune diseases that potentially relapsing, exception: Subjects with autoimmune-related hypothyroidism requiring stable dose thyroxine replacement only are eligible; Subjects with type I diabetes mellitus controlled on a stable insulin regimen are eligible; 14) Subjects who have received systemic corticosteroids (> 10 mg/day prednisone equivalent) or other systemic immunosuppressants (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF drugs) within 4 weeks prior to the initiation of study treatment, but excluded Locally, ocularly, intra-articularly, intranasally, or inhaled corticosteroids; Subjects receiving acute low-dose sys
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety evaluation index;MTD/RP2D and Dose Limited Toxicity (DLT);RP2D; | — |
Secondary
| Measure | Time frame |
|---|---|
| PK characteristics;Efficacy evaluation index; | — |
Countries
Republic of China
Contacts
Public ContactJin Li
Shanghai East Hospital
Outcome results
None listed