Inclusion Criteria:
- Histologically confirmed diagnosis of a solid tumor malignancy with homozygous
deletion of the MTAP gene detected in tumor tissue or ctDNA
- Unresectable or metastatic disease.
- Patients must have received standard therapies appropriate for their tumor type and
stage with disease progression on or after the most recent treatment.
1. Phase 1 dose escalation, RECIST 1.1 measurable or evaluable disease
2. Phase 1b and Phase 2 cohorts, RECIST 1.1 measurable disease.
- Presence of a tumor lesion amenable to mandatory biopsy for pharmacodynamic
evaluation at baseline and on-study unless Sponsor-confirmed as medically unsafe or
infeasible.
- Age ≥ 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Adequate organ function
Exclusion Criteria:
- Prior treatment with a PRMT5 or MAT2A inhibitor therapy.
- Active brain metastases or carcinomatous meningitis.
- History of significant hemoptysis or hemorrhage within 4 weeks of the first dose of
study treatment.
- Major surgery within 4 weeks of first dose of study treatment.
- History of intestinal disease, inflammatory bowel disease, major gastric surgery, or
other gastrointestinal conditions (eg, uncontrolled nausea, vomiting, malabsorption
syndrome) likely to alter absorption of study treatment or result in inability to
swallow oral medications
- Cardiac abnormalities
