Advanced or Metastatic Solid Tumors, Breast Cancer, Colorectal Cancer, Endometrial Cancer, Extensive Stage Small Cell Lung Cancer (ES-SCLC), Head and Neck Cancers, NSCLC, Ovarian Cancer, Prostate Cancer
Conditions
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, ES-SCLC, SCLC, Extensive Stage Small Cell Lung Cancer
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.
Interventions
DRUGIDE-161
Oral Medication
DRUGPembrolizumab
Intravenous Infusion
Sponsors
IDEAYA Biosciences
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Sequential
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Contacts
STUDY_DIRECTORDarrin Beaupre, MD,PhD
IDEAYA Biosciences
Outcome results
None listed