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

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to characterize the safety, tolerability, and efficacy of IDE161.

Detailed 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.

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

Conditions
-----------------
Advanced or Metastatic Solid Tumors, Breast Cancer, Ovarian Cancer, Pancreas Cancer, Prostate Cancer

Intervention / Treatment
-----------------
* Drug: IDE-161


Participation Criteria
=================
Eligibility Criteria
-----------------
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 Exclusion Criteria: 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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Sequential
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Module 1 Part 1: Monotherapy Dose Escalation<br>Participants will be assigned to a dose level. | Drug: IDE-161<br>* Oral medication taken daily<br>|
| Experimental: Module 1 Part 2: Monotherapy Dose Expansion<br>After a dose is decided in Part 1, participants entering part 2 will be assigned to a dose level. | Drug: IDE-161<br>* Oral medication taken daily<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 (Dose Escalation): To characterize the safety and tolerability of IDE161 monotherapy by evaluating the number of participants with dose limiting toxicities, adverse events, and laboratory abnormalities as graded by NCI CTCAE version 5.0 | Incidence of Dose Limiting Toxicities Incidence of treatment-emergent Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing | 6 months | 
| Part 2 (Dose Expansion): To further characterize the safety and tolerability of IDE161 monotherapy by evaluating the number of participants dose limiting toxicities, adverse events, and laboratory abnormalities as graded by NCI CTCAE version 5.0 | Further assess the safety and tolerability of IDE161 monotherapy at the Recommended Dose for Expansion (RDE) by evaluating: Incidence of Dose Limiting Toxicities Incidence of treatment-emergent Adverse Events as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), timing, seriousness, and relationship to study therapy Laboratory abnormalities as characterized by type, frequency, severity (as graded by NCI CTCAE version 5.0), and timing | Approximately 1 year | 
| Part 2 (Dose Expansion): To evaluate preliminary preliminary anti-tumor activity of IDE161 monotherapy in participants by measuring tumor Overall Response Rate using RECIST criteria v1.1 | Tumor response: Overall Response Rate assessed using RECIST criteria v1.1 | Approximately 2 year | 
| Part 2 (Dose Expansion): To evaluate preliminary anti-tumor activity of IDE161 monotherapy in participants by measuring Duration of Response using RECIST criteria v1.1 | Tumor response: Duration of Response assessed using RECIST criteria v1.1 | Approximately 2 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1 (Dose Escalation): To evaluate the preliminary anti-tumor activity of IDE161 monotherapy in participants by measuring tumor Overall Response Rate using RECIST criteria v1.1 | Tumor response: Overall Response Rate assessed using RECIST criteria v1.1 | Approximately 2 years | 
| Part 1 (Dose Escalation): To evaluate the preliminary anti-tumor activity of IDE161 monotherapy in participants by measuring Duration of Response using RECIST criteria v1.1 | Tumor response: Duration of Response assessed using RECIST criteria v1.1 | Approximately 2 years | 
| Maximal Plasma Concentration (Cmax) of IDE161 in Part 1 & Part 2 | PK parameters of IDE161 and metabolite over time at Cycle 1 Day 1 and at steady state (Cycle 1 Day 15) to model maximum concentration (Cmax) with trough levels at the beginning of every Cycle thereafter | Approximately 1 year | 
| ime to Achieve Maximal Plasma Concentration (Tmax) of IDE161 in Part 1 & Part 2 | PK parameters of IDE161 and metabolite over time at Cycle 1 Day 1 and at steady state (Cycle 1 Day 15) to model time to maximum concentration (Tmax) with trough levels at the beginning of every Cycle thereafter | Approximately 1 year | 
| Area Under the Plasma Concentration Versus Time Curve (AUC) of IDE161 | PK parameters of IDE161 and metabolite over time at Cycle 1 Day 1 and at steady state (Cycle 1 Day 15) to model Area Under the the Plasma Concentration Versus Time Curve (AUC) with trough levels at the beginning of every Cycle thereafter | Approximately 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
PARPi, PARP inhibitor, BRCA, HRD gene alteration, Breast, Ovarian, Advanced solid tumors, Metastatic solid tumors, BRCA 1, BRCA 2, Homologous recombination, PARG, PARG Inhibition, ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51C, RAD51D, RAD54L, NBN, FANCA, HRD+