A PARG Inhibitor DAT-2645 Monotherapy in Patients with Advanced/Metastatic Solid Tumors Harboring BRCA1/2 Loss of Function Alterations And/or Other Defects in the DDR Pathway

Exclusion Criteria

• •Patients who received systemic chemotherapy, small-molecule targeted drugs within 14 days or 5 half-lives (whichever is longer) prior to the first dose of study drug.
• •Patients who received biological anti-tumor drugs (including immunotherapy, target therapy, antibody-drug conjugate \[ADC\]) within 4 weeks prior to the first dose of the study drug.
• •Patients who have undergone major surgery within 4 weeks prior to the first dose of study drug.
• •Patients who have received radiotherapy within 4 weeks prior to the first dose of study drug (palliative radiotherapy for non-target lesions could be acceptable if it was performed before 14 days prior to the first dose of study drug).
• •Any previous treatment with a PARG inhibitor.
• •Patients with active CNS metastases (patients with asymptomatic CNS metastases which are imaging stable and not require steroid treatment within 28 days prior to the first dose of study drug, and previous treated breast cancer brain metastasis, can only be enrolled in the Part 2 study).
• •Patients who have second primary malignant tumors within the past 3 years prior to screening, except for those who have been cured of basal cell carcinoma, cervical carcinoma in situ, or breast carcinoma in situ.
• •Patients with clinically significant cardiovascular or cerebrovascular diseases.
• •Active uncontrolled infections requiring intravenous antibiotics or hospitalization.
• •Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of DAT-2645 and no history of bowel obstruction within 6 months prior to enrollment.
• •Known pulmonary interstitial disease or pulmonary interstitial fibrosis.
• •Patients known hypersensitivity to any component or excipient of DAT-2645.
• •Any unresolved toxicities from any prior therapy with severity great than CTCAE Grade 1 prior to start of DAT-2645, except for alopecia and pigmentation and Grade 2 of peripheral sensory neuropathy.
• •Participated in other clinical trials (except for screening failure) within 4 weeks prior to the first dose of the study drug in this study.
• •Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (active HBV infection is defined as positive hepatitis B surface antigen \[HbsAg\], or HBV DNA exceeding the lower limit of detection; active HCV infection is defined as positive anti-HCV antibody, and HCV RNA exceeding the lower limit of detection).
• •Known human immunodeficiency virus (HIV) infection (patients with adequate CD4+ T cell counts and without history of acquired immune deficiency syndrome \[AIDS\]-defining opportunistic infections could be enrolled after consultation with sponsor).
• •Women who are pregnant or breastfeeding.
• •History or evidence of any other clinically significant condition or disease (with the exception of those outlined above) that, in the opinion of the investigator, would be a risk to patient safety or interfere with the study evaluation, procedures or completion.