Overview
This is a Phase 1, open-label, multicenter, dose escalation and expansion study of the safety, PK, PD, and preliminary anti-tumor activity of IDE397 as a single agent and in combination with other anticancer agents including taxanes (docetaxel, paclitaxel), or sacituzumab govitecan (SG), in adult patients with selected advanced or metastatic MTAP-deleted advanced solid tumors who are unresponsive to standard of care therapy. IDE397 is a small molecule inhibitor of methionine adenosyltransferase 2 alpha (MAT2A).
Eligibility
Inclusion Criteria:
- Participant must be at least 18 years of age
- Advanced or metastatic solid tumor that has progressed on at least one prior line of treatment or is intolerant to additional effective standard therapy
- Have evidence of homozygous loss of MTAP or MTAP deletion
- Willing to undergo paired fresh biopsy (pre- and post-treatment) procedure. Exceptions may be made for feasibility and safety concerns
- Measurable disease
- ECOG performance status <= 1
- Adequate organ function
- Able to swallow and retain orally administered study treatment
- Recovery from acute effects of prior therapy
- Able to comply with contraceptive/barrier requirements
Exclusion Criteria:
- Known symptomatic brain metastases
- Known primary CNS malignancy
- Current active liver or biliary disease
- Impairment of gastrointestinal (GI) function
- Active uncontrolled infection
- Clinically significant cardiac abnormalities
- Previous treatment with a MAT2A inhibitor and / or PRMT inhibitor or sacituzumab govitecan
- Systemic anti-cancer therapy or major surgery within 4 weeks prior to study entry
- Radiation therapy within 2 weeks prior to study entry
- Prior irradiation to >25% of the bone marrow
- Current use or anticipated need for food or drugs that are known strong CYP3A4/5 inhibitors or inducers
- Currently receiving another investigational study drug.
- Known or suspected hypersensitivity to IDE397/excipients or components