Study of IDE397 in Participants With Solid Tumors Harboring MTAP Deletion

Study Overview
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Brief Summary
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This is a Phase 1, open-label, multicenter, dose escalation and expansion study of the safety, PK, PD, and anti-tumor activity of IDE397 as a single agent and in combination with docetaxel or paclitaxel, in adult patients with selected advanced or metastatic MTAP-deleted advanced solid tumors who are unresponsive to standard of care therapy or for whom no curative therapy is available. IDE397 is a small molecule inhibitor of methionine adenosyltransferase 2 alpha (MAT2A).

Official Title
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An Open Label, Phase 1, Treatment Study to Evaluate the Safety, Pharmacokinetics and Pharmacodynamics of IDE397 (MAT2A Inhibitor) In Adult Participants With Advanced Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Drug: IDE397
* Drug: Docetaxel
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be at least 18 years of age Advanced or metastatic solid tumor that has progressed on at least one prior line of treatment or is intolerant to additional effective standard therapy Have evidence of homozygous loss of MTAP or MTAP deletion Willing to undergo paired fresh biopsy (pre- and post-treatment) procedure. Exceptions may be made for feasibility and safety concerns Measurable disease ECOG performance status <= 1 Adequate organ function Able to swallow and retain orally administered study treatment Recovery from acute effects of prior therapy Able to comply with contraceptive/barrier requirements Exclusion Criteria: Known symptomatic brain metastases Known primary CNS malignancy Current active liver or biliary disease Impairment of gastrointestinal (GI) function Active uncontrolled infection Clinically significant cardiac abnormalities Previous treatment with a MAT2A inhibitor and / or PRMT inhibitor Systemic anti-cancer therapy or major surgery within 4 weeks prior to study entry Radiation therapy within 2 weeks prior to study entry Prior irradiation to >25% of the bone marrow Current use or anticipated need for food or drugs that are known strong CYP3A4/5 inhibitors or inducers Currently receiving another investigational study drug. Known or suspected hypersensitivity to IDE397/excipients or components

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Dose Escalation Monotherapy (Solid Tumors)<br> | Drug: IDE397<br>* IDE397 dosed orally<br>|
| Experimental: Part 2: Monotherapy Dose Expansion (NSCLC, EG and Urothelial)<br> | Drug: IDE397<br>* IDE397 dosed orally<br>|
| Experimental: Part 3: Combination Dose Escalation with docetaxel or paclitaxel (NSCLC, EG and Urothelial)<br> | Drug: IDE397<br>* IDE397 dosed orally<br>Drug: Docetaxel<br>* Intravenous infusion<br>Drug: Paclitaxel<br>* Intravenous infusion<br>|
| Experimental: Part 4: Combination Dose Expansion with docetaxel or paclitaxel (NSCLC, EG and Urothelial)<br> | Drug: IDE397<br>* IDE397 dosed orally<br>Drug: Docetaxel<br>* Intravenous infusion<br>Drug: Paclitaxel<br>* Intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting Toxicities (DLTs) of IDE397 | Incidence of DLTs of IDE397 will be determined | 21 days following the first dose of IDE397 | 
| Dose-limiting Toxicities (DLTs) of IDE397 in combination with either docetaxel or paclitaxel | Incidence of DLTs of IDE397 in a combination setting will be determined | 21 - 28 days following the first dose of IDE397 | 
| Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of IDE397 | MTD and RP2D of IDE397 will be determined | Approximately 2 years | 
| Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of IDE397 in combination with either docetaxel or paclitaxel | MTD and RP2D of IDE397 in a combination setting will be determined | Approximately 2 years | 
| To evaluate preliminary anti-tumor activity of IDE397 in combination expansion arms | Objective Response Rate (ORR) and Duration of Response (DoR) | Approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Pharmacokinetics of IDE397 and metabolite | Pharmacokinetics of IDE397 and metabolite following single and multiple oral administration as a single agent and in combination with either docetaxel or paclitaxel, will be determined | Approximately 2 years | 
| Drug interaction between IDE397 and docetaxel or paclitaxel | Pharmacokinetics of docetaxel or paclitaxel. | Approximately 2 years | 
| Pharmacodynamic effect of IDE397 as a single agent and in combination with either docetaxel or paclitaxel | Changes in the levels of MAT2A pathway and PRMT5 pathway will be determined | Approximately 2 years | 
| Preliminary anti-tumor activity in IDE397 escalation and combination escalation arms | Objective response rate and duration of response will be assessed by Investigator using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1) | Approximately 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SAM, MAT2A, 9p21, CDKN2A, MTAP, Solid Tumors, PRMT5, Synthetic Lethality, Inhibitor, MTAP deletion, CDKN2A deletion, MAT2A Inhibitor, Advanced solid tumors, Lung Cancer, Bladder Cancer, Squamous, NSCLC, Urothelial Cancer, Non small cell, Docetaxel, Paclitaxel