A Study to Evaluate YF087 in Subjects With MSI-H or dMMR Advanced Solid Tumors

An Open-Label, Multicenter, Phase I Dose-Finding and Expansion Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of YF087 in Patients With Microsatellite Instability-High (MSI-H) or Mismatch Repair-Deficient (dMMR) Advanced Solid Tumors

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.

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;