Locally advanced or metastatic solid tumors carrying KRAS G12D mutations
Conditions
Interventions
Dose escalation stage and safety cohort expansion stage:HBW-012336 Capsules
Dose cohort expansion stage:HBW-012336 Capsules
Sponsors
Sun Yat-sen University Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: Patients must meet all of the following inclusion criteria to be enrolled in this study: 1) Age >= 18 years old, gender not limited; 2)Patients with KRAS G12D mutant solid tumors (including but not limited to pancreatic cancer, colorectal cancer, lung cancer, endometrial cancer, etc.) who are locally advanced or metastatic and unresectable by histopathology and/or cytology and have failed or been intolerant to at least first-line standard treatment, or have no standard treatment available; Note: A written test report confirming the positivity of KRAS G12D mutation is required; The test results of KRAS G12D in tumor tissues from the research center or outside the hospital within 3 years before the enrollment of patients with KRAS G12D mutant advanced solid tumors are acceptable, or the test results of KRAS G12D in blood, pleural effusion or other samples containing cancer cells or DNA. 3) According to RECIST version 1.1, there is at least one measurable tumor lesion; 4) The ECOG score is 0 to 1. 5) The expected survival time is >= 3 months; 6) Have good organ functions; 7) The blood pregnancy test of women of childbearing age within 7 days before the first administration is negative, or they have no fertility potential (have undergone surgical sterilization such as hysterectomy, bilateral salpingectomy and/or bilateral oophorectomy or have reached menopause); Women of childbearing age and their male partners, as well as male patients and their female partners, agree to use an effective contraceptive plan within 6 months from the signing of the informed consent form until the end of the last medication use, and the men have no sperm donation plans and the women have no egg donation plans. 8) Understand and voluntarily sign the ICF, and have the willingness and ability to complete regular visits, treatment plans, laboratory tests and other trial processes.
Exclusion criteria
Exclusion criteria: Patients with any of the following items cannot be enrolled in this study: 1) Previously received inhibitors targeting KRAS G12D mutations; 2) Have received anti-tumor treatments such as radiotherapy, chemotherapy, biological therapy, targeted therapy or immunotherapy within 4 weeks prior to the first administration, except for the following: · Nitrosamuras and mitomycin C are within 6 weeks before the first use of the investigatory drugs; · Oral fluorouracil, endocrine therapy drugs and small molecule targeted drugs should be taken within 2 weeks before the first use of the investigational drug or within 5 half-lives of the drug (whichever is longer). · For traditional Chinese medicine with anti-tumor indications, palliative radiotherapy or local treatment within 2 weeks before the first use of the investigational drug; 3) Received clinical trial drug treatment within 4 weeks before the first administration; 4) Had undergone grade 3 or 4 surgery within 4 weeks before the first administration (as defined in the "Administrative Measures for the Grading of Surgeries in Medical Institutions", see Appendix 5) (excluding puncture biopsy), or needed to undergo elective surgery during the study period, or had not fully recovered from previous surgeries; 5) Received systemic corticosteroids (prednisone > 10mg/ day or equivalent doses of similar drugs) or other immunosuppressants for more than 7 days within 2 weeks before the first administration or during the study period; Except for the following circumstances: · Treatment with local, ocular, intra-articular, intranasal and inhaled glucocorticoids; · Short-term use of glucocorticoids for preventive treatment (such as preventing contrast agent allergy); 6) Those who receive attenuated live vaccines within 4 weeks before the first administration or are planned to receive them during the study period; 7) Drugs that may affect the metabolism of this product have been used within 2 weeks before the first administration, such as strong inhibitors of CYP3A4 or P-gp or BCRP (clarithromycin, ritonavir, ketoconazole, voriconazole, etc.), or strong inducers (rifampicin, carbamazepine, phenytoin, etc.); 8) Those who have received allogeneic hematopoietic stem cell transplantation or organ transplantation in the past; 9) Those who have been severely infected within 4 weeks before the first administration, or have shown any signs or symptoms of active infection within 2 weeks, or require antibiotic treatment within 2 weeks (except for prophytically administered antibiotics); A fever of unknown cause >= 38.3? or a body temperature >= 38.0? that persists for more than one hour within 24 hours before the first administration, but the fever caused by the tumor is judged by the researcher, can be enrolled. 10) There are active central nervous system (CNS) metastatic lesions; Subjects with previously treated brain metastases (such as those undergoing surgery or radiotherapy) are allowed to be enrolled if they have clinical stability after treatment (clinical stability is defined as: no disease progression >= 4 weeks as evaluated by imaging), and corticosteroid hormones are discontinued 4 weeks before the administration of the investigational drug. Untreated and asymptomatic subjects with brain metastases (i.e., no neurological symptoms, no need for corticosteroid hormones, no long diameter of any brain metastases >1.5 cm, and no obvious edema around the brain metastases) can be enrolled; 11) Have a serious histor
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety and tolerance;Maximum tolerated dose, MTD; | — |
Secondary
| Measure | Time frame |
|---|---|
| Validity;PK characteristics; | — |
Countries
China
Contacts
Public ContactRuihua Xu
Sun Yat-sen University Cancer Center
Outcome results
None listed