Locally advanced or metastatic solid tumors
Conditions
Interventions
Experimental group:The dose escalation phase (Phase Ib) was a dose escalation study of D-1553 tablets combined with GH21 capsules for the treatment of patients with locally advanced or metastatic soli
Sponsors
Zhejiang Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. The patient or their legal representative can understand and voluntarily sign the written informed consent form (before starting this study and any research procedures); 2. Age >= 18 years old, gender not limited; 3. In the dose escalation stage (Ib phase): Patients with locally advanced or metastatic solid tumors carrying KRASG12C mutations, who have failed standard treatment or have no standard treatment or are intolerant to standard treatment. 4. Dose expansion stage (II phase): Queue 1: Patients with locally advanced or metastatic non-small cell lung cancer that has not been treated with KRASG12C inhibitors and who have PD-L1 expression TPS score 3 months; 7. ECOG score 0-1; 8. The patient must have adequate organ function, defined as follows: Blood, without granulocyte colony-stimulating factor support within 14 days, absolute neutrophil count (ANC) >= 1.5×10^9/L; 14 days without blood transfusion, without using thrombopoietin (TPO) and interleukin-11 (IL-11), platelets >= 100×10^9/L; 14 days without blood transfusion, without using erythropoietin (EPO), hemoglobin >= 90 g/L; Kidney, serum creatinine = 60 ml/min or estimated eGFR >= 60 ml/min using the MDRD equation; Liver, albumin >= 3.0 g/dL; Total bilirubin <= 1.5×ULN; If liver metastasis, total bilirubin <= 2.5×ULN; AST/ALT <= 2.5×ULN; If liver metastasis, AST/ALT <= 5×ULN; Coagulation function, international normalized ratio (INR) and prothrombin time (PT) <= 1.5×ULN, unless the patient is receiving anticoagulant treatment (INR < 2.5×ULN), and PT or PTT are within the expected treatment range of the anticoagulant; Activated partial thromboplastin time (APTT) <= 1.5×ULN, unless the patient is receiving anticoagulant treatment (APTT < 2.5×ULN), and PT or PTT are within the expected treatment range of the anticoagulant. 9. Male patients with fertility and female patients of childbearing age must agree to take reliable contraceptive measures (hormonal or barrier method or abstinence) from signing the informed consent form until 6 months after the last administration of the study drug (unless the patient is receiving anticoagulant treatment, INR < 2.5×ULN, and PT or PTT are within the expected treatment range of the anticoagulant). The pregnancy test result of female patients within <= 7 days before the first administration of the study drug must be negative.
Exclusion criteria
Exclusion criteria: 1. Biological agents that have received chemotherapy or anti-tumor treatment within 3 weeks prior to the first administration, and have received radiotherapy, endocrine therapy or other anti-tumor drug treatments within 4 weeks prior to the first administration, except for the following: Nitrosoureas or Mitomycin C are within 6 weeks prior to the first use of the study drug; Oral fluorouracil derivatives, small molecule targeted drugs, and Chinese herbal or patent medicine with anti-tumor indications are within 5 half-lives or 2 weeks prior to the first use of the study drug (whichever is shorter); Local palliative radiotherapy is within 2 weeks prior to the first use of the study drug; 2. Have received other off-patent clinical research drugs or treatments within 5 half-lives or 4 weeks prior to the first administration (whichever is shorter); 3. Have undergone major organ surgery (excluding biopsy) or experienced significant trauma within 4 weeks prior to the first administration, or require elective surgery during the trial; 4. Have used CYP3A4 or P-gp inhibitors or inducers within 2 weeks prior to the first administration or 4 half-lives prior to the first administration (whichever is shorter); 5. Have evidence of the following heart diseases: Within 6 months prior to the first administration, acute myocardial infarction, unstable angina pectoris, coronary artery bypass grafting, cerebrovascular accident or transient ischemic attack; At the screening stage, determined as grade III-IV heart failure according to the New York Heart Association classification; At the screening stage, echocardiography (ECHO) shows left ventricular ejection fraction (LVEF) = 450ms (male), >= 470ms (female); At the screening stage, there is still poorly controlled hypertension (systolic blood pressure >= 160mmHg and/or diastolic blood pressure >= 100mmHg) after drug treatment; 6. Have difficulty swallowing or have gastrointestinal diseases or other absorption disorders that affect drug absorption, such as intestinal obstruction, Crohn's disease, ulcerative colitis, short bowel syndrome, gastric emptying disorder, or have severe gastrointestinal-related toxicity before the first administration and have not recovered to grade 2 or below; Or have been diagnosed with clinically significant or acute gastrointestinal diseases; 7. Have uncontrolled pleural effusion, pericardial effusion or need for repeated drainage of pleuroperitoneal fluid (once a month or more frequently); 8. Have active brain metastases or patients with active symptoms of central nervous system metastasis, including headache, vomiting and dizziness, only patients with CNS lesions and treated or untreated asymptomatic patients without symptoms for more than 2 weeks after treatment are eligible: There are measurable lesions outside the CNS according to RECIST v1.1; Stable brain metastases after treatment, defined as no disease progression or bleeding evidence within 28 days before treatment start and at least 14 days of discontinuation of steroid hormones and other treatment drugs before enrollment; 9. Have interstitial pneumonia within 6 months prior to the first administration, or any evidence of clinical active interstitial lung disease; 10. Have experienced thromboembolic events such as cerebrovascular accident (including transient ischemic attack), deep vein thrombosis and pulmonary embolism within 6 months pri
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Phase Ib: Adverse events (AE), severity, vital signs, physical examination, electrocardiogram, abnormal laboratory indicators, etc.;Phase Ib: Incidence of dose-limiting toxicity (DLT);Phase II: Objective response rate (ORR) assessed by the Independent Imaging Evaluation Committee (IRC) according to RECIST 1.1; | — |
Countries
China
Contacts
Public ContactZhengbo Song
Zhejiang Cancer Hospital
Outcome results
None listed