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

Phase 1

Recruiting

• Conditions: Advanced or Metastatic Solid Tumors; Breast Cancer; Endometrial Cancer; Colorectal Cancer; Head and Neck Cancers; Ovarian Cancer; Prostate Cancer; Nsclc
• Interventions: Drug: IDE-161; Drug: Pembrolizumab

• Registration Number: NCT05787587
• Lead Sponsor: IDEAYA Biosciences

Brief Summary

The purpose of this study is to characterize the safety, tolerability, and efficacy of IDE161 as a single agent and in combination with pembrolizumab.

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 and in combination with pembrolizumab in participants with advanced/recurrent endometrial cancer.

Study Timeline

• Study First Submitted: 2023-03-17
• Study First Submitted QC: 2023-03-27
• Study First Posted: 2023-03-28
• Study Start: 2023-04-05
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-31
• Last Update Posted: 2025-04-02
• Primary Completion: 2026-10
• Study Completion: 2027-05

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 216

Inclusion Criteria

1. Adult participants must be 18 years of age or older

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

3. For Module 1 only, Have documented evidence of BRCA1/2 and/or genetic alterations conferring homologous recombination deficiency (HRD) (ATM, BARD1, BRIP1, CDK12, CHEK1, CHEK2, FANCL, PALB2, PPP2R2A, RAD51B, RAD51C, RAD51D, RAD54L, NBN, FANCA)

   For Module 2 only, results of MSI and/or MMR testing required.

   For Module 2 only, results of BRCA1/2 and HRD gene testing required.

4. 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

5. For Module 2 only, advanced or metastatic Endometrial Cancer (uterine carcinosarcoma is excluded)

6. For Module 2 only, Must have progressed on treatment with an anti-PD-1/L1 monoclonal antibody (MAB)

Exclusion Criteria

1. Known primary CNS malignancy
2. Impairment of GI function or GI disease that may significantly alter the absorption of IDE161
3. Have active, uncontrolled infection
4. Clinically significant cardiac abnormalities
5. Major surgery within 4 weeks prior to enrollment
6. Radiation therapy within 2 weeks prior to enrollment
7. Systemic cytotoxic chemotherapy within 4 weeks prior to enrollment
8. Radioimmunotherapy within 6 weeks of enrollment
9. Treatment with a therapeutic antibody within 4 weeks prior to enrollment
10. Treatment with an anti-cancer small molecule within 5 half-lives (t1/2), or 2 weeks, whichever is shorter
11. Have current active liver or biliary disease
12. For Module 2 only, History or allogeneic tissue/solid organ transplant
13. For Module 2 only, Active autoimmune disease that has required systemic treatment in past 2 years
14. For Module 2 only, History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Module 1 Part 1: Monotherapy Dose Escalation	IDE-161	Participants will be assigned to a dose level.
Module 1 Part 2: Monotherapy Dose Expansion	IDE-161	After a dose is decided in Part 1, participants entering part 2 will be assigned to a dose level.
Module 2 Part 1: Combination Dose Escalation with pembrolizumab	IDE-161	Participants will be assigned to a dose level.
Module 2 Part 1: Combination Dose Escalation with pembrolizumab	Pembrolizumab	Participants will be assigned to a dose level.
Module 2 Part 2: Combination Dose Expansion with pembrolizumab	IDE-161	After a dose is decided in Part 1, participants entering part 2 will be assigned to a dose level.
Module 2 Part 2: Combination Dose Expansion with pembrolizumab	Pembrolizumab	After a dose is decided in Part 1, participants entering part 2 will be assigned to a dose level.

Primary Outcome Measures

Name	Time	Method
Part 1 (Dose Escalation): To characterize the safety and tolerability of IDE161 monotherapy or in combination with pembrolizumab to determine the MTD and/or RDE	Approximately 2 years	* 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
Part 2 (Dose Expansion): To further assess the safety and tolerability of IDE monotherapy and in combination with pembrolizumab at the RDE	Approximately 4 years	* Incidence of treatment-emergent AEs 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 v5.0), and timing
Part 2 (Dose Expansion): To evaluate preliminary anti-tumor activity of IDE161 monotherapy or in combination with pembrolizumab	Approximately 4 years	Tumor response: Overall Response Rate assessed using RECIST criteria v1.1

Secondary Outcome Measures

Name	Time	Method
Part 2 (Dose Expansion) Assess the risk/benefit at an IDE161 monotherapy dose and exposure alternative to the initial expansion dose; as well as an IDE161 dose in combination with a fixed dose of pembrolizumab and exposure alternative to the initial	Approximately 4 years	Descriptively compare the totality of emerging data (efficacy, safety, PK, PD) between the initial expansion dose cohort and dose optimization cohort
To characterize the single dose PK Peak Plasma Concentration (Cmax) of IDE161 monotherapy and in combination with pembrolizumab.	Approximately 4 years	Single-dose PK parameters of IDE161
To characterize the multiple dose PK Peak Plasma Concentration (Cmax) of IDE161 monotherapy and in combination with pembrolizumab.	Approximately 4 years	Multiple-dose PK parameters of IDE161
To characterize the single dose PK Area under the plasma concentration versus time curve (AUC) of IDE161 monotherapy and in combination with pembrolizumab.	Approximately 4 years	Single-dose PK parameters of IDE161
To characterize the multiple dose PK Area under the plasma concentration versus time curve (AUC) of IDE161 monotherapy and in combination with pembrolizumab.	Approximately 4 years	Multiple-dose PK parameters of IDE161
To characterize the single dose PK Time to Peak drug Concentration (Tmax) of IDE161 monotherapy and in combination with pembrolizumab.	Approximately 4 years	Single-dose PK parameters of IDE161
To characterize the multiple dose PK Time to Peak drug Concentration (Tmax) of IDE161 monotherapy and in combination with pembrolizumab.	Approximately 4 years	Multiple-dose PK parameters of IDE161

Trial Locations

Locations (24)

HonorHealth Research Institute; 🇺🇸 Phoenix, Arizona, United States

The Angeles Clinic; 🇺🇸 Los Angeles, California, United States

Hoag Memorial Hospital; 🇺🇸 Newport Beach, California, United States

California Pacific Medical Center; 🇺🇸 San Francisco, California, United States

Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

Orlando Health; 🇺🇸 Orlando, Florida, United States

Emory University; 🇺🇸 Atlanta, Georgia, United States

OSF St Francis Medical Center; 🇺🇸 Peoria, Illinois, United States

Indiana University; 🇺🇸 Indianapolis, Indiana, United States

Dana Faber Cancer Institute; 🇺🇸 Boston, Massachusetts, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

Comprehensive Cancer Centers of Nevada; 🇺🇸 Las Vegas, Nevada, United States

Roswell Park Comprehensive Cancer Center; 🇺🇸 Buffalo, New York, United States

Columbia University Medical Center; 🇺🇸 New York, New York, United States

Weil Cornell University; 🇺🇸 New York, New York, United States

Sarah Cannon Research Institute - Oklahoma University; 🇺🇸 Oklahoma City, Oklahoma, United States

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Sarah Cannon Research Institute - Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States

MD Anderson; 🇺🇸 Houston, Texas, United States

NEXT Oncology; 🇺🇸 Fairfax, Virginia, United States

START Mountain Region; 🇺🇸 West Valley City, Utah, United States

Swedish Cancer Institute; 🇺🇸 Seattle, Washington, United States

University of Wisconsin; 🇺🇸 Madison, Wisconsin, United States