Advanced Solid Tumor Cancer
Conditions
Brief summary
This is an open-label, multicenter clinical study to evaluate the safety, tolerability, and pharmacokinetics of YF087 in subjects with Microsatellite Instability-High (MSI-H) or Mismatch Repair-Deficient (dMMR) advanced solid tumors.
Interventions
DRUGYF087
Dosage form: Tablet • Administration route: Oral, once a day
Sponsors
InventisBio Co., Ltd
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with locally advanced (unresectable) or metastatic solid tumors; * dMMR/MSI-H status demonstrated in tumor tissue, blood, or other samples containing cancer cells or DNA; * Subjects must have experienced disease progression after the most recent therapy for advanced disease (prior therapy must include at least one PD-1/PD-L1 inhibitor treatment). * Presence of at least 1 measurable lesion that can be measured by CT or MRI based on RECIST V1.1 criteria; * ECOG≤1
Exclusion criteria
* Prior treatment with a WRN inhibitor such as HRO760, RO7589831, GSK4418959 and NDI-219216; * Prior to the first dose of study intervention, receipt of any anticancer treatment (including chemotherapy, targeted therapy, immunotherapy, etc.) or any other investigational medicinal product within 14 days or 3 half-lives (whichever is shorter); * Subjects with unstable or symptomatic or progressive central nervous system (CNS) metastases and/or leptomeningeal carcinomatosis and/or brainstem metastases and/or spinal cord compression; * Subjects with clinically significant cardiovascular and cerebrovascular disease * Subjects with concomitant medical conditions that the investigator believes may increase the risk of toxicity, such as serious cardiovascular, respiratory or neurological diseases; * Use of, or planned use of, any of the following medications that has not been discontinued for at least 14 days or 5 half-lives (whichever is shorter) before the first study drug administration: 1. Strong CYP3A4 inducers or inhibitors; 2. Drugs known to prolong the QT interval. * Pregnant or lactating females;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects participants with adverse events | From enrollment to 30 days after last dose | Number of subjects participants with adverse events |
| Subject incidence of Dose-limiting toxicities (DLT) | From enrollment to Cycle 1 Day 21 | — |
| Objective response rate (ORR) | From enrollment to the end of treatment, about 1 year | — |
Secondary
| Measure | Time frame |
|---|---|
| Disease control rate (DCR)-assessed by IRC and investigators | From enrollment to the end of treatment, about 1 year |
| Progression free survival (PFS) | From enrollment to the end of treatment, about 1 year |
| Duration of Response (DOR) | From enrollment to the end of treatment, about 1 year |
| Change from baseline in QT/QTc interval | On Cycle 0 Day 1 and Cycle 2 Day 1 (Cycle 0 is 7 days and the rest cycle is 21 days) |
| Primary PK parameters: area under the concentration-time curve from the time of dosing to time t (AUC0-t) | From Cycle 0 Day 1 to Cycle 0 Day 7 and on Cycle 2 Day 1 (Cycle 0 is 7 days and the rest cycle is 21 days) |
| Primary PK parameters: area under the concentration-time curve from time 0 to infinity (AUC0-∞) | From Cycle 0 Day 1 to Cycle 0 Day 7 and on Cycle 2 Day 1 (Cycle 0 is 7 days and the rest cycle is 21 days) |
| Primary PK parameters: Mean residence time (MRT) | From Cycle 0 Day 1 to Cycle 0 Day 7 and on Cycle 2 Day 1 (Cycle 0 is 7 days and the rest cycle is 21 days) |
| Primary PK parameters: maximum concentration (Cmax) | From Cycle 0 Day 1 to Cycle 0 Day 7 and on Cycle 2 Day 1 (Cycle 0 is 7 days and the rest cycle is 21 days) |
| Primary PK parameters: Time to maximum concentration (Tmax) | From Cycle 0 Day 1 to Cycle 0 Day 7 and on Cycle 2 Day 1 (Cycle 0 is 7 days and the rest cycle is 21 days) |
| Primary PK parameters: t1/2 | From Cycle 0 Day 1 to Cycle 0 Day 7 and on Cycle 2 Day 1 (Cycle 0 is 7 days and the rest cycle is 21 days) |
| Primary PK parameters: Apparent Volume of Distribution (Vz/F) | From Cycle 0 Day 1 to Cycle 0 Day 7 and on Cycle 2 Day 1 (Cycle 0 is 7 days and the rest cycle is 21 days) |
Contacts
CONTACTYuting Li
PRINCIPAL_INVESTIGATORRuihua Xu, MD
Sun Yat-sen University Cancer Center (SYSUCC)
Outcome results
None listed