Advanced solid tumor with RAS mutation
Conditions
Interventions
Part 1: dose escalation.:XS-03 tablets, 2 mg, 5 mg, 10mg, 20 mg, 40mg, 60mg, 80mg (adjusted according to actual climbing conditions), were taken orally once and observed for 3 days (Cycle 0)
Each Cycle D1-5, D15-19, once a day, orally, 28 days for 1 cycle (cycle 1-N).
Part 2: dose expansion.:XS-03 tablets, MTD or RP2D (choose 1-2 dose levels), D1-5, D15-19 per cycle, once a day, orally, 28 days for 1 treatment cycle.
Sponsors
Beijing Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: Patients must meet all of the following inclusion criteria: 1) Volunteer to participate in clinical trials and sign informed consent. 2)18= Age =75 years old, regardless of gender. 3) Patients with locally advanced or metastatic solid tumors confirmed by histologically or cytologically after failure of adequate standard therapy or no effective standard therapy, patients with advanced colorectal cancer were preferentially enrolled in the dose expansion stage. 4) Patients are required to provide a written tumor gene test report to confirm RAS mutation before enrollment: They can be enrolled according to the genetic test report issued by a previously qualified genetic testing institution; For patients without previous reports, tumor tissue samples should be provided to the central laboratory for genetic testing (if there is no previous archived sample and the researchers judge that it is not possible to re-biopsy the sample, peripheral blood samples are allowed to be taken to the central laboratory for ctDNA testing), and the results are used to enter the group. 5) At least one non-intracranial measurable lesion (based on RECIST V1.1). 6) Eastern cooperative oncology group (ECOG) Physical status score 0-1. 7) The expected survival time is =3 months. 8) The patient has adequate organ and bone marrow function. 9) Female subjects of reproductive age in the screening period had negative serological pregnancy test results within 7 days prior to dosing. Subjects also agreed to use a reliable method of contraception from the time they signed the informed consent until 6 months after the last dosing. This includes, but is not limited to: abstinence from sex, vasectomy for men, sterilization for women, effective Iuds, and effective contraceptive drugs.
Exclusion criteria
Exclusion criteria: Patients who meet any of the following conditions are not allowed to enter this clinical study: 1) Received chemotherapy, small molecule targeted therapy, and endocrine therapy within 2 weeks before the first dose. Patients who had received tumor immunotherapy, antibodies, or polypeptide antitumor drugs within 4 weeks prior to initial administration. 2) Patients who had undergone therapeutic procedures other than diagnosis, biopsy, or drainage within 4 weeks prior to initial dosing, or who expected to undergo major surgery during the study period. For subjects who have had drainage (e.g., chest cavity, biliary tract, etc.) and/or had a drainage tube placed within 4 weeks prior to dosing, the relevant symptoms/signs should have been substantially relieved without prophylactic/therapeutic antibiotic use. 3) Patients who had received radiotherapy within 4 weeks prior to initial dosing. 4) Toxicity from previous antitumor therapy had not recovered (> NCI-CTCAE 5.0 grade 1), and alopecia, pigmentation, neurotoxicity, or other toxicity that the investigators assessed had become chronic and did not affect the safety of the investigational medication returned to NCI-CTCAE 5.0 grade 2 or below. 5) Imaging (CT or MRI) shows that the tumor has invaded large blood vessels (such as aorta, pulmonary artery, pulmonary vein, vena cava, etc.) or is at risk of bleeding (such as esophageal and gastric varices). 6) Patients with central nervous system metastasis who meet any of the following conditions: a) Need to undergo local treatment (surgery, radiation or other); b) Taking steroids >10mg prednisone/day (or equivalent) before enrollment; c) Continuous use of antiepileptic drugs is required; d) There is meningeal, midbrain, pontine, bulbar or spinal cord metastasis. Only patients with brain metastases who are asymptomatic and do not require treatment are admitted. 7)A history of serious cardiovascular disease, including but not limited to the following: a) Severe heart rhythm or conduction abnormalities that require clinical intervention; b) Acute coronary syndrome, congestive heart failure, myocardial infarction, unstable angina pectoris, coronary/peripheral artery bypass grafting, cerebral infarction, cerebral hemorrhage, pulmonary embolism, deep vein thrombosis (within 3 months prior to initial administration), or other serious cardiovascular events within 6 months prior to initial administration; c) New York Heart Association (NYHA) heart function grade =II; d) Left ventricular ejection fraction (LVEF) 450ms (male) or > 470ms (female). 8) A serious infection requiring intravenous antibiotics, antivirals, or hospitalization within 2 weeks prior to initial administration; Or there is currently an active infection. 9) Have difficulty swallowing or a gastrointestinal disorder that interferes with drug absorption and is in an acute episode (such as Crohn's disease, ulcerative colitis, or short bowel syndrome) or other malabsorption condition. 10) A known history of pulmonary interstitial disease, pulmonary fibrosis, or pneumonia due
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of Dose limiting toxicity (DLT) (DLT observation period).;Maximum tolerated dose (MTD) and/or Recommended Dose for Phase II clinical studies (RP2D).;Objective response rate (ORR); | — |
Secondary
| Measure | Time frame |
|---|---|
| Other safety endpoints: adverse events during treatment; Proportion of patients with serious adverse events, deaths, dosing adjustments or discontinuation due to drug toxicity; The frequency and severity of other safety test abnormalities (such as laboratory tests, vital signs, physical examinations, electrocardiograms, etc.);PK parameters after single and multiple oral administration of XS-03 tablets; Efficacy end point: Objective Response Rate (ORR), Disease Control Rate (DCR), Duration of Overall Response, DOR, Time to response (TTR), progression-free survival (PFS), overall survival (OS).;Other efficacy endpoints: DCR, DOR, TTR, PFS, OS; | — |
Countries
China
Contacts
Public ContactShen Lin
Beijing Cancer Hospital
Outcome results
None listed