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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Breast Cancer; Colorectal Cancer; Ovarian Cancer; NSCLC; Prostate Cancer; Endometrial Cancer; Advanced or Metastatic Solid Tumors; Head and Neck Cancers; Extensive Stage Small Cell Lung Cancer (ES-SCLC)
• Intervention / Treatment: Drug: Pembrolizumab; Drug: IDE-161

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 Type: Interventional
• Enrollment (Estimated): 216
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic
    • Newport Beach, California, United States, 92663
      • Hoag Memorial Hospital
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale University
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Faber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Karmanos Cancer Institute
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Comprehensive Cancer Centers of Nevada
  • New York
    • Buffalo, New York, United States, 14203
      • Roswell Park Comprehensive Cancer Center
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10065
      • Weil Cornell University
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Sarah Cannon Research Institute - Oklahoma University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Sarah Cannon Research Institute - Thomas Jefferson University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Houston, Texas, United States, 77030
      • MD Anderson
    • Irving, Texas, United States, 75039
      • NEXT Oncology
    • San Antonio, Texas, United States, 78229
      • NEXT Oncology
  • Utah
    • West Valley City, Utah, United States, 84119
      • START Mountain Region
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • NEXT Oncology
  • Washington
    • Seattle, Washington, United States, 98104
      • Swedish Cancer Institute
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Module 1 Part 1: Monotherapy Dose Escalation; Participants will be assigned to a dose level.	Drug: IDE-161; Oral Medication
Experimental: Module 1 Part 2: Monotherapy Dose Expansion; After a dose is decided in Part 1, participants entering part 2 will be assigned to a dose level.	Drug: IDE-161; Oral Medication
Experimental: Module 2 Part 1: Combination Dose Escalation with pembrolizumab; Participants will be assigned to a dose level.	Drug: Pembrolizumab; Intravenous Infusion; Other Names: KEYTRUDA®; Drug: IDE-161; Oral Medication
Experimental: Module 2 Part 2: Combination Dose Expansion with pembrolizumab; After a dose is decided in Part 1, participants entering part 2 will be assigned to a dose level.	Drug: Pembrolizumab; Intravenous Infusion; Other Names: KEYTRUDA®; Drug: IDE-161; Oral Medication

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 or in combination with pembrolizumab to determine the MTD and/or RDE	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 2 years
Part 2 (Dose Expansion): To further assess the safety and tolerability of IDE monotherapy and in combination with pembrolizumab at the RDE	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	Approximately 4 years
Part 2 (Dose Expansion): To evaluate preliminary anti-tumor activity of IDE161 monotherapy or in combination with pembrolizumab	Tumor response: Overall Response Rate assessed using RECIST criteria v1.1	Approximately 4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Descriptively compare the totality of emerging data (efficacy, safety, PK, PD) between the initial expansion dose cohort and dose optimization cohort	Approximately 4 years
To characterize the single dose PK Peak Plasma Concentration (Cmax) of IDE161 monotherapy and in combination with pembrolizumab.	Single-dose PK parameters of IDE161	Approximately 4 years
To characterize the multiple dose PK Peak Plasma Concentration (Cmax) of IDE161 monotherapy and in combination with pembrolizumab.	Multiple-dose PK parameters of IDE161	Approximately 4 years
To characterize the single dose PK Area under the plasma concentration versus time curve (AUC) of IDE161 monotherapy and in combination with pembrolizumab.	Single-dose PK parameters of IDE161	Approximately 4 years
To characterize the multiple dose PK Area under the plasma concentration versus time curve (AUC) of IDE161 monotherapy and in combination with pembrolizumab.	Multiple-dose PK parameters of IDE161	Approximately 4 years
To characterize the single dose PK Time to Peak drug Concentration (Tmax) of IDE161 monotherapy and in combination with pembrolizumab.	Single-dose PK parameters of IDE161	Approximately 4 years
To characterize the multiple dose PK Time to Peak drug Concentration (Tmax) of IDE161 monotherapy and in combination with pembrolizumab.	Multiple-dose PK parameters of IDE161	Approximately 4 years

Collaborators and Investigators

• Sponsor: IDEAYA Biosciences
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Darrin Beaupre, MD,PhD, IDEAYA Biosciences

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2023
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: March 17, 2023
• First Submitted That Met QC Criteria: March 27, 2023
• First Posted (Actual): March 28, 2023

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: PARP inhibitor; Pembrolizumab; PD-L1; Breast; PALB2; Extensive Stage Small Cell Lung Cancer; ES-SCLC; SCLC; Ovarian; MSS; Endometrial; Advanced solid tumors; BRCA; MMR; PARPi; GIS; Metastatic solid tumors; CDK12; MSI; BRCA 1; BRCA 2; ATM; RAD51C; RAD51D; BARD1; BRIP1; FANCA; CHEK2; NBN; RAD54L; HR genes; Pembro; HRD gene alteration; Homologous recombination; PARG; PARG Inhibition; CHEK1; FANCL; PPP2R2A; HRD+; genomic instability score; GI+; gLOH; genomic loss of heterozygosity
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Endocrine System Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Uterine Diseases; Genital Diseases, Female; Endocrine Gland Neoplasms; Colonic Diseases; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Gonadal Disorders; Skin Diseases; Breast Diseases; Uterine Neoplasms; Skin and Connective Tissue Diseases; Prostatic Neoplasms; Colorectal Neoplasms; Ovarian Neoplasms; Breast Neoplasms; Head and Neck Neoplasms; Endometrial Neoplasms; Mental Retardation, X-Linked, With Or Without Seizures, Arx-Related; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: IDE161-001; KEYNOTE-F86 (Other Identifier: Merck Sharp & Dohme LLC); MK-3475-F86 (Other Identifier: Merck Sharp & Dohme LLC)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No