A Study of PARG Inhibitor FORX-428 in Patients With Advanced Solid Tumors.

The goal of this interventional study is to evaluate the safety and tolerability of escalating doses of FORX-428 as monotherapy in patients with select advanced solid tumors with BRCA1/2 mutations or other DDR deficiencies or high replication stress, and to determine the maximum tolerated dose (MTD) and Recommended Cohort Expansion Dose (RCED) of FORX-428 as monotherapy.

Inclusion Criteria: 1. Patient must be \>/=18 years of age at time of signing informed consent; 2. Patient has histologically and/or cytologically confirmed diagnosis of advanced or metastatic selected solid tumors. 3. Patient must have progressed on at least 1 prior line of therapy in the advanced or metastatic setting that is considered an appropriate standard of care. In general, if maintenance therapy is part of the standard of care, it should be considered as part of the "1 prior line of therapy in the advanced or metastatic setting" requirement; 4. Patient must fulfill genomic selection criteria: prior available documented evidence in tissue or blood (circulating tumor DNA \[ctDNA\]) of the genetic alterations indicated below. The Sponsor Medical Monitor or delegate must confirm eligibility based on the reported genomic alteration and applicable assay cut off criteria prior to patient enrollment. • Patients with BRCA1/2 mutations (germline or somatic, pathogenic or likely pathogenic) and other mutations signifying HR deficiency or high replication stress. • For Dose Expansion: Tumor types for Dose Expansion cohorts include a subset of tumors specified in Inclusion Criterion 3 as follows: i) Cohort 1: Advanced or metastatic breast cancer independent of hormone receptor status and documented evidence of prior treatment with a locally approved PARP inhibitor(s); ii) Cohort 2: Advanced or metastatic ovarian cancer with prior available documented evidence in tissue or blood (ctDNA) of specific genomic abnormalities. iii) Cohort 3: Advanced or metastatic breast cancer with prior available documented evidence in tissue or blood (ctDNA) of specific genomic abnormalities. Note: Diagnostic genetic testing for Dose Escalation/backfilling and Dose Expansion cohorts must meet the following requirements: • United States (US): Testing must have been performed using a College of American Pathologists/Clinical Laboratory Improvement Amendments (CAP/CLIA)-certified laboratory developed test (LDT) or a Food and Drug Administration (FDA)-approved diagnostic test. 5. Patient has measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 at Clinical Screening; Note: Tumor lesions situated in a previously irradiated or otherwise locally treated area will be considered measurable provided that there has been clear imaging-based progression of the lesion since the time of local treatment. 6. Patient has adequate bone marrow and organ function, defined by the following laboratory results obtained within 14 days before first dose of study drug: * Platelet count \>/=100 × 10\^9/L (\>/=100,000/μL) (absence of platelet transfusion within 1 week); * Hemoglobin \>/=90 g/L (\>/=5.6 mmol/L) (absence of red blood cell transfusion within 2 weeks); * Absolute neutrophil count \>/=1.5 × 10\^9/L (\>/=1500/μL) (absence of growth factors within 2 weeks); * Aspartate aminotransferase and alanine aminotransferase \