A Study of PARG Inhibitor ETX-19477 in Patients With Advanced Solid Malignancies

Inclusion Criteria:

• Males and females of age ≥ 18 years at the time of signing the informed consentdocument.

• Histologically or cytologically confirmed advanced (incurable recurrent,unresectable, or metastatic) solid cancer, excluding primary central nervous system (CNS) tumors.

• Any solid tumor malignancy, excluding primary CNS tumors, with progression on orafter or intolerance to most recent systemic therapy. Preferential enrollmentconsideration will be made for patients with known BRCA2 mutations resulting in lossof function.

• Progression on or after or intolerance to most recent systemic therapy. Priortreatment in the recurrent/metastatic setting; patients must have received approvedstandard therapy that is available to the patient that is known to confer clinicalbenefit, unless this therapy is contraindicated, intolerable to the patient, or isdeclined by the patient.

• No investigational agent within 3 weeks or 5 half-lives (whichever is shorter;minimum of 2 weeks) prior to first dose of study drug.

• Life expectancy of at least 3 months.

Exclusion Criteria:

• Receiving continuous corticosteroids at prednisone-equivalent dose of >10 mg/day.Chronic systemic corticosteroid therapy for physiologic replacement (≤10 mg/day ofprednisone equivalents) and the use of non-systemic corticosteroids (e.g., inhaled,topical, intra-nasal, intra-articular, or ophthalmic) are permitted.

• Definitive radiotherapy within 6 weeks and palliative radiation within 2 weeks priorto the first dose of study drug.

• Symptomatic untreated or progressing brain metastases. Stable, treated brainmetastases are allowed if no evidence of radiologic or clinical progression orincreasing corticosteroid use for at least 4 weeks.

• Impairment of gastrointestinal (GI) function or GI disease that may significantlyalter the absorption of ETX-19477 and no history of bowel obstruction within 6months prior to enrollment.

• Known symptomatic and radiologically progressing or leptomeningeal disease (LMD). IfLMD has been reported radiographically on baseline magnetic resonance imaging (MRI),but is not suspected clinically by the Investigator, the patient must be free ofneurological symptoms of LMD.

• Resting ECG with QT interval calculated using the Fridericia's formula (QTcF) >470msec on 2 or more timepoints within a 24-hour period, or history or family historyof congenital long QT syndrome.

• History of myocardial infarction or unstable angina within 6 months prior toenrollment, or clinically significant cardiac disease, such as ventriculararrhythmia requiring therapy, uncontrolled hypertension, clinically significantuncontrolled arrhythmias, or any history of symptomatic congestive heart failure.

• Known active or chronic infection (viral, bacterial, or fungal), includingtuberculosis, hepatitis B, hepatitis C, or AIDS-related illness. Controlledinfections, including HIV and "cured" hepatitis C (no active fever, no evidence ofsystemic inflammatory response syndrome) that are stable with undetectable viralload on antiviral treatment are not exclusionary.

• Acute or chronic uncontrolled renal disease, pancreatitis, or liver disease (withexception of patients with Gilbert's Syndrome, asymptomatic gallstones, livermetastases, or stable chronic liver disease per Investigator assessment).

• Known other previous/current malignancy requiring treatment within ≤2 years exceptfor limited disease treated with curative intent, such as carcinoma in situ,squamous or basal cell skin carcinoma, or superficial bladder carcinoma.

• Patients receiving proton pump inhibitors (PPIs), strong cytochrome P450 (CYP)3Ainhibitors and inducers, or P-glycoprotein (P-gp) inhibitors. Patients should notreceive PPIs within 7 days prior to first dose of study drug. Strong CYP3A inducersor inhibitors or strong P-gp inhibitors should not be given within 6 half-livesprior to first dose of study drug.

• Patients currently treated with therapeutic doses of warfarin sodium (Coumadin®) orany other coumarin-derivative anticoagulants