Title
A Study of PARG Inhibitor IDE161 in Participants With Advanced Solid Tumors

Description
The purpose of this study is to characterize the safety, tolerability including determination of maximum tolerated dose (MTD), maximum accepted dose (MAD), recommended dose(s) for expansion (RDE) and/or recommended Phase 2 dose (RP2D), pharmacokinetics (PK), pharmacodynamics (PD) and preliminary anti-tumor activity of IDE161 as a single agent in participants with advanced or metastatic solid tumors harboring BRCA1/2 loss of function alterations and/or other defects in the homologous recombination (HR) pathway.

Objective
Primary Objectives:
-Part 1 (Dose Escalation): To characterize the safety and tolerability of IDE161 monotherapy to determine the MTD/MAD and/or RDE
-Part 2 (Dose Expansion): To further assess the safety and tolerability of IDE161 monotherapy at the RDE
-Part 2: To evaluate preliminary anti-tumor activity of IDE161 monotherapy

Secondary Objectives:
-Part 1: To evaluate preliminary anti-tumor activity of IDE161 monotherapy
-Part 2: Assess risk/benefit at an IDE161 monotherapy dose and exposure alternative to the initial expansion dose
-Both parts: To characterize the single and multiple dose PK of IDE161 monotherapy

Treatment The purpose of this study is to characterize the safety, tolerability, and efficacy of IDE161.

Key Eligibility Inclusion Criteria:

Adult participants must be 18 years of age or older

Advanced or metastatic solid tumors excluding primary central nervous system (CNS) tumors

Have documented evidence of genetic alterations conferring homologous recombination deficiency

Participant must have progressed on at least one prior line of therapy in the advanced or metastatic setting that is considered an appropriate standard of care, or for which the participant has documented intolerance

Known primary CNS malignancy

Impairment of GI function or GI disease that may significantly alter the absorption of IDE161

Have active, uncontrolled infection

Clinically significant cardiac abnormalities

Major surgery within 4 weeks prior to enrollment

Radiation therapy within 2 weeks prior to enrollment

Systemic cytotoxic chemotherapy within 4 weeks prior to enrollment

Radioimmunotherapy within 6 weeks of enrollment

Treatment with a therapeutic antibody within 4 weeks prior to enrollment

Treatment with an anti-cancer small molecule within 5 half-lives (t1/2), or 2 weeks, whichever is shorter

Applicable Disease Sites
Anal; Bladder; Breast; Cervix; Colon and Rectum; Endocrine cancers; Esophagus; Gastrointestinal cancers, other; Genitourinary cancers, other; Head and Neck; Hematologic cancers, other; Ill-Defined Sites; Kidney; Liver; Lung; Melanoma/Skin cancer; Ovary; Pancreas; Prostate; Sarcoma; Stomach; Thyroid; Unknown Sites; Uterus

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital