Clinical trial NCT05787587: A Study of PARG Inhibitor IDE161 in Participants With Advanced Solid Tumors
Official title: A Study of PARG Inhibitor IDE161 in Participants With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced or Metastatic Solid Tumors
Breast Cancer
Ovarian Cancer
Prostate Cancer
Endometrial Cancer
Colorectal Cancer
Head and Neck Cancers
Nsclc
Keywords: 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+
Endometrial
Pembro
Pembrolizumab
HR genes
genomic instability score
GIS
GI+
gLOH
genomic loss of heterozygosity
MSS
MSI
MMR
PD-L1
Lead sponsor: IDEAYA Biosciences
Sponsor class: INDUSTRY
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2023-03-28
Enrollment: 216
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Sequential
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Approximately 2 years
measure: Part 2 (Dose Expansion): To further assess the safety and tolerability of IDE monotherapy and in combination with pembrolizumab at the RDE
timeFrame: Approximately 4 years
measure: Part 2 (Dose Expansion): To evaluate preliminary anti-tumor activity of IDE161 monotherapy or in combination with pembrolizumab
timeFrame: Approximately 4 years
Secondary outcomes:
measure: 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
timeFrame: Approximately 4 years
measure: To characterize the single dose PK Peak Plasma Concentration (Cmax) of IDE161 monotherapy and in combination with pembrolizumab.
timeFrame: Approximately 4 years
measure: To characterize the multiple dose PK Peak Plasma Concentration (Cmax) of IDE161 monotherapy and in combination with pembrolizumab.
timeFrame: Approximately 4 years
measure: To characterize the single dose PK Area under the plasma concentration versus time curve (AUC) of IDE161 monotherapy and in combination with pembrolizumab.
timeFrame: Approximately 4 years
measure: To characterize the multiple dose PK Area under the plasma concentration versus time curve (AUC) of IDE161 monotherapy and in combination with pembrolizumab.
timeFrame: Approximately 4 years
measure: To characterize the single dose PK Time to Peak drug Concentration (Tmax) of IDE161 monotherapy and in combination with pembrolizumab.
timeFrame: Approximately 4 years
measure: To characterize the multiple dose PK Time to Peak drug Concentration (Tmax) of IDE161 monotherapy and in combination with pembrolizumab.
timeFrame: Approximately 4 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: HonorHealth Research Institute
state: Arizona
city: Los Angeles
country: United States
facility: The Angeles Clinic
state: California
city: Newport Beach
country: United States
facility: Hoag Memorial Hospital
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: Denver
country: United States
facility: Sarah Cannon Research Institute
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Orlando
country: United States
facility: Orlando Health
state: Florida
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Peoria
country: United States
facility: OSF St Francis Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Boston
country: United States
facility: Dana Faber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Buffalo
country: United States
facility: Roswell Park Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: New York
country: United States
facility: Weil Cornell University
state: New York
city: Oklahoma City
country: United States
facility: Sarah Cannon Research Institute - Oklahoma University
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Sarah Cannon Research Institute - Thomas Jefferson University
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: Irving
country: United States
facility: NEXT Oncology
state: Texas
city: San Antonio
country: United States
facility: NEXT Oncology
state: Texas
city: West Valley City
country: United States
facility: START Mountain Region
state: Utah
city: Fairfax
country: United States
facility: NEXT Oncology
state: Virginia
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: IDEAYA Biosciences
name: Darrin Beaupre, MD,PhD
role: STUDY_DIRECTOR
References: