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.
Eligibility criteria
This trial does not accept healthy volunteers
Qualifiers
Are ≥ 18 years of age (or the minimum age of consent in accordance with local regulations) at the time of signing the ICF.
Have a histologically confirmed diagnosis of a locally advanced recurrent or metastatic solid tumor type of interest with MTAP deletion (for dose escalation: mesothelioma [pleural or peritoneal], gastroesophageal cancers [squamous and adenocarcinoma of esophagus, gastric adenocarcinoma, gastroesophageal junction cancers], pancreatic adenocarcinoma and biliary tract carcinomas (intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer), NSCLC [adenocarcinoma, squamous cell carcinoma, and adeno-squamous] or UC [including mixed urothelial-squamous histology]; for dose expansion: NSCLC that has progressed on at least one prior line of treatment and for which additional effective standard therapy is not available or for which the participant is not a candidate due to intolerance).
Are willing and able to provide blood/tumor tissue samples for biomarker testing. An archival tumor tissue specimen must be provided for central confirmation of MTAP loss.
Must be willing and able to provide the blood/serum/plasma samples
Disqualifiers
Known symptomatic brain metastases requiring supraphysiologic doses of systemic corticosteroids
Have a known primary central nervous system (CNS) malignancy
Have had other malignancies within 2 years prior to the first dose, with some exceptions
Impaired cardiac function or clinically significant cardiac diseases
Trial design
Design model
Sequential
Treatments tested in this trial
IDE892
Drug
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
Drug
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.
Treatment groups
260 Participants
are divided into 4 treatment groups
Group A: Part 1: IDE892 Monotherapy Dose Escalation (MTAP-deleted advanced solid tumors)Experimental treatment 1 intervention
Group B: Part 2: IDE892 Monotherapy Dose Expansion (MTAP-Deleted NSCLC)Experimental treatment 1 intervention
Group C: Part 3: IDE892 + IDE397 Combination Dose Escalation (MTAP-Deleted Solid Tumors)Experimental treatment 2 interventions
Group D: Part 4: IDE892 + IDE397 Combination Dose Expansion (MTAP-Deleted NSCLC)Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Incidence 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)
2
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)
3
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
Secondary outcomes
1
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
2
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
3
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)
4
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)
Other outcomes
Sponsors and contacts
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