This is a multicenter clinical study to evaluate the safety, efficacy, and Pharmacokinetics (PK) of IDE892 as monotherapy and in combination with other agents including IDE397 in participants with methylthioadenosine phosphorylase (MTAP)-deleted advanced solid tumors within indications of interest.
The purpose of this study is to evaluate safety, efficacy, and PK of IDE892 as monotherapy and combination therapy in adult participants with MTAP-deleted tumors who have progressed after standard therapy and represent a high unmet need. In the current stage, the combination will be focused on IDE892 with IDE397, an oral inhibitor of methionine adenosyltransferase 2A (MAT2A), to fully exploit the vulnerabilities associated with methylthioadenosine (MTA) accumulation in MTAP-deleted tumors while maintaining a substantial therapeutic index. The mechanistic rationale for this study is discussed in the following sections.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
260
IDE892 is an inhibitor of the Protein arginine methyltransferase 5 (PRMT5) that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions.
IDE397 is an oral MAT2A inhibitor that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions. In this study, IDE397 will be evaluated in combination with IDE892 (Parts 3 and 4) in participants with MTAP-deleted advanced solid tumors.
NEXT Oncology Houston
Houston, Texas, United States
RECRUITINGNEXT Oncology Dallas
Irving, Texas, United States
RECRUITINGNEXT Oncology Virginia
Fairfax, Virginia, United States
RECRUITINGIncidence of Dose-limiting Toxicities (DLTs) of IDE892 (Parts 1 and 3)
Incidence of DLTs of IDE892 will be determined in Parts 1 and 3
Time frame: 21 days following the first dose of IDE892 (each cycle is 21 days)
Incidence of AEs and SAEs (Parts 1, 2, 3, and 4)
Incidence and severity of adverse events (AEs)/serious adverse events (SAEs) (graded based on Common Terminology Criteria for Adverse Events \[CTCAE\] version 5.0) will be determined in Parts 1, 2, 3, and 4.
Time frame: From first dose until 28 days after last dose (each cycle is 21 days)
Objective response rate (ORR) and duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Parts 2 and 4)
Objective response rate (ORR: best objective response of complete response \[CR\] + partial response \[PR\]) and duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the Investigator
Time frame: Approximately 2 years
Overall response rate (ORR) and duration of response (DOR) per RECIST version 1.1 (Parts 1 and 3)
ORR and DOR per RECIST version 1.1 as assessed by the Investigator
Time frame: Approximately 2 years
Disease control rate (DCR) and duration of stable disease per RECIST version 1.1 (Parts 1, 2, 3, and 4)
Disease control rate (disease control rate \[DCR\]: CR + PR + stable disease \[SD\]) and duration of SD per RECIST version 1.1 as assessed by the Investigator
Time frame: Approximately 2 years
Maximum Observed Plasma Concentration (Cmax) (Parts 1, 2, 3, and 4)
Cmax is the highest observed plasma concentration of the study drug following administration of IDE892 as a single agent or in combination with IDE397
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Time to Maximum Observed Concentration (Tmax)
Time to Maximum Observed Concentration (Tmax) after administration of IDE892 as a single agent or in combination with IDE397
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast)
AUClast reflects total drug exposure from dosing until the last measurable concentration after administration of IDE892 as a single agent or in combination with IDE397
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Time of Last Quantifiable Concentration (Tlast)
Tlast is the time at which the final measurable drug concentration is observed after administration of IDE892 as a single agent or in combination with IDE397
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf)
AUCinf represents total drug exposure extrapolated to infinite time after administration of IDE892 as a single agent or in combination with IDE397
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Terminal Elimination Half-Life (t½)
t½ is the time required for the plasma concentration of the drug to decrease by half during the terminal elimination phase after administration of IDE892 as a single agent or in combination with IDE397
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
Cmax,ss is the maximum observed plasma concentration after achieving steady state after administration of IDE892 as a single agent or in combination with IDE397
Time frame: Cycle 1 Day 15 (each cycle is 21 days)
Time to Maximum Concentration at Steady State (Tmax,ss)
Tmax,ss is the time from dosing to Cmax at steady state after administration of IDE892 as a single agent or in combination with IDE397
Time frame: Cycle 1 Day 15 (each cycle is 21 days)
Trough Plasma Concentration at Steady State (Ctrough)
Ctrough is the concentration obtained immediately prior to the next scheduled dose at steady state after administration of IDE892 as a single agent or in combination with IDE397
Time frame: Cycle 1 Day 15 (each cycle is 21 days)
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUCtau)
AUCtau represents drug exposure over one full dosing interval at steady state after administration of IDE892 as a single agent or in combination with IDE397
Time frame: Cycle 1 Day 15 (each cycle is 21 days)
Apparent Clearance (CL/F)
CL/F is the apparent clearance of the drug after extravascular dosing after administration of IDE892 as a single agent or in combination with IDE397
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Apparent Volume of Distribution (Vz/F)
Vz/F is the apparent volume of distribution following extravascular dosing after administration of IDE892 as a single agent or in combination with IDE397
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Accumulation Ratio (Rac)
Rac is calculated as the ratio of AUC or Cmax at steady state compared with first dose, reflecting drug accumulation after administration of IDE892 as a single agent or in combination with IDE397
Time frame: Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.