A Study of TSN1611 Treating Patients with Advanced Solid Tumors Harboring KRAS G12D Mutation

The study is a first-in-human (FIH), open-label, multi-center phase 1/2 study of TSN1611 in subjects with KRAS G12D mutant advanced solid tumors. This study will consist of a phase 1 dose escalation part and phase 2 dose expansion part.

TSN1611 is a KRAS G12D inhibitor.

The study is non-randomized with sequential assignment:

Experimental - Phase 1- Dose-finding/evaluation of TSN1611 monotherapy: The phase 1 part will evaluate the prespecified sequential dose levels of TSN1611 in subjects with KRAS G12D mutant advanced solid tumors to determine the recommended dose of TSN1611 for further investigation. TSN1611 will be administered at the assigned dose level, orally, until disease progression or intolerable toxicity.

Experimental - Phase 2 - Dose expansion of TSN1611 monotherapy: Phase 2 part will evaluate the efficacy and safety of TSN1611 as monotherapy at the recommended dose level in separate groups of patients with pancreatic cancer, colorectal cancer, non-small cell lung cancer, or other solid tumors, harboring KRAS G12D mutations. TSN1611 will be administered at the assigned dose level, orally, until disease progression or intolerable toxicity.

Inclusion criteria:

• Subjects with histologically or cytologically confirmed locally advanced or metastatic solid tumor harboring KRAS G12D mutation; subjects must be refractory or intolerable to standard treatment, or have no standard treatment available, etc.

Exclusion Criteria:

• Leptomeningeal disease or Active central nervous system (CNS) metastases.
• History of interstitial lung disease (ILD), drug induced IDL, or current active pneumonitis, radiation pneumonitis requiring therapeutic intervention, or uncontrolled other lung disease.
• Any of the following in the past 6 months: myocardial infarction, unstable angina, symptomatic congestive heart failure, stroke or transient ischemic attack, pulmonary embolism.
• Prior treatment with KRAS G12D targeted therapy.