Advanced solid tumor of highly microsatellite unstable type (MSI-H)
Conditions
Interventions
Experimental group (Phase la dose escalation, single arm open study):Usage and dosage: Oral administration
Take once a day, with a dosage of 50mg per dose, 150mg per dose, 300mg per dose, 600mg per dose, and 900mg per dose during period Ia, for a total of 5 groups
The dosage of each dose taken during the Ib period is subject to the results of the Ia study.
Medication schedule: single administration, with a 21 day dosing cycle.
FS-207 monotherapy for MSI-H late stage CRC patients with ICIs treatment failure/intolerance (Phase Ib dose extension):The dosage of each dose taken during the Ib period is subject to the results of t
FS-207 monotherapy for other MSI-H advanced solid tumor patients (including gastric cancer/gastroesophageal junction adenocarcinoma or endometrial cancer) who have failed/are intolerant to ICIs treatm
Sponsors
Beijing Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Male or female patients aged >= 18 years at the time of signing the informed consent form 2. Diagnosed by histology or cytology as locally advanced or metastatic solid tumors (non resectable, including but not limited to CRC, gastric cancer/gastroesophageal junction adenocarcinoma, and endometrial cancer), participants who have undergone disease progression or intolerance after receiving standard treatment in the past must meet the following criteria: having received at least one immune checkpoint inhibitor (ICIs) treatment in the past, and being judged as treatment failure or toxicity intolerance due to disease progression (if participants have no further standard treatment plan or refuse to receive other standard treatments after meeting the above ICIs treatment failure/intolerance criteria, they also meet the inclusion criteria of this article) 3 participants must provide a positive test report for MSI-H/dMMR status in tumor tissue (previous test results must have a test report from a tertiary hospital or a suitable qualified institution). At the same time, participants must provide archived tumor tissue samples within 5 years that meet the quantity requirements for MSI-H status testing (if unable to provide, fresh tumor biopsy samples must be provided) 4. Eastern Cooperative Oncology Group (ECOG) physical condition score: 0-1 points; 5. Expected survival period >= 3 months; 6. Have at least one measurable lesion (according to RECIST V1.1 standards, measurable lesions are defined as non lymph node lesions with a longest diameter >= 10mm or lymph node lesions with a short diameter >= 15mm measured by CT or MRI) 7. The main organ functions are good, that is, the relevant examination indicators meet the following requirements: (1) no use of hematopoietic stimulating factors, no blood transfusion or blood products, no use of albumin or blood products, etc. within 14 days before the test, hemoglobin >= 90 g/L, neutrophil count >= 1.5 × 10^9/L, platelet count >= 90 × 10^9/L; (2) total bilirubin = 50 mL/min (estimated according to Cockcroft Gault formula) can be enrolled (note: creatinine clearance rate needs to be confirmed only when serum creatinine is higher than 1.5 times the upper limit of the normal reference range); (4) International normalized ratio (INR) and prothrombin time <= 1.5 × ULN (unless anticoagulation with warfarin is being used). 8. Female or male participants with fertility must agree to take effective contraception (including one or more non pharmacological contraceptive measures) or safety measures within 3 months from the date of signing the informed consent form until the last treatment of the trial; 9. Agree to comply with the requirements and procedures of clinical trials and voluntarily sign an informed consent form.
Exclusion criteria
Exclusion criteria: 1. Known to have Werner syndrome 2. Previously received drug treatment targeting Werner syndrome helicase (WRN); Have received any anti-tumor treatment (including chemotherapy, targeted therapy, immunotherapy, etc.) within 3 weeks or 5 half lives before the first administration (whichever is longer), including mitomycin and nitrosourea within 6 weeks before the first administration; fluorouracil oral drugs within 2 weeks before the first administration, and small molecule drugs within 2 weeks or 5 half lives before the first administration, whichever is longer); Have received Chinese medicine or traditional Chinese patent medicines and simple preparations with clear anti-tumor indications 1 week before the first administration; Received potent inhibitors/inducers of P-glycoprotein (P-gp) within 4 weeks or 5 half lives prior to the first administration (whichever is longer) Patients with adverse reactions related to previous anti-tumor treatments that have not yet recovered to <= grade 1 (according to NCI CTCAE V6.0) are excluded from toxicity that the researchers have determined to have no safety risk, such as hair loss, grade 2 peripheral neurotoxicity, stable hypothyroidism after hormone replacement therapy, mild rash, pigmentation, etc. The specific situation is determined by the researchers; Within 4 weeks prior to the first administration, significant surgery (excluding establishing vascular access, biopsy via laparoscopy, mediastinoscopy, or thoracoscopy) or curative radiation therapy (palliative radiation therapy within 2 weeks prior to the first administration) has been performed or planned to be performed during the trial period 7. Meningeal metastasis; Patients with clinical symptoms of central nervous system metastasis or other evidence indicating uncontrolled central nervous system metastasis are deemed unsuitable for inclusion by the researchers. Asymptomatic or stable brain metastasis patients can be enrolled, but they must also meet the following conditions: (1) Imaging examination shows no evidence of progression at least 4 weeks before the first administration; (2) If you have received local treatment for brain metastasis in the past (such as radiotherapy, surgery, etc.), it must have been completed at least 14 days before the first administration; (3) Within 14 days prior to the first administration, neurological symptoms are stable and there is no need to use steroid drugs, or prednisone (or equivalent) with a stable steroid drug dose of <= 10 mg/day Researchers have identified patients with unstable pleural, peritoneal, or pericardial effusion accompanied by obvious symptoms (those who have stable clinical symptoms after treatment with pleural, peritoneal, or pericardial effusion may be included in the study) 9 Have suffered from other active malignant tumors within 3 years before the first administration (except for localized tumors that have received radical treatment, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, prostate carcinoma in situ, cervical carcinoma in situ, and breast carcinoma in situ; malignant tumors that have suffered from any other malignant tumor in the past but have undergone radical surgery and have not recurred for 3 years after surgery can be considered to be included in the group); In the Ia climbing stage, patients with stable condition of the second primary tumor can also be enrolled if the researchers determine it. 10. According to the rese
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events during treatment (TEAE);The incidence, severity, and correlation of serious adverse events (SAEs);Incidence of dose limiting toxicity (DLT);Other safety assessments, including abnormal laboratory tests, 12 lead electrocardiograms, etc; | — |
Secondary
| Measure | Time frame |
|---|---|
| The PK parameters of FS-207 tablets include but are not limited to peak concentration, peak time, elimination half-life, clearance rate, apparent volume of distribution, steady-state peak concentration, steady-state peak time, steady-state trough concentration, and area under the steady-state blood drug concentration time curve;Researchers evaluated the objective response rate, disease control rate, time to response, duration of response, progression free survival, and survival based on the solid tumor efficacy evaluation criteria v1.1; | — |
Countries
China
Contacts
Public ContactShen Lin
Beijing Cancer Hospital
Outcome results
None listed