Clinical Trials /

Study of IDE397 in Participants With Solid Tumors Harboring MTAP Deletion

NCT04794699

Description:

This is a Phase 1, open-label, multicenter, multiple dose, dose escalation study of the safety, PK, PD, and anti-tumor activity of IDE397 as a single agent 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.

Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of IDE397 in Participants With Solid Tumors Harboring MTAP Deletion
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: IDE397-001
  • NCT ID: NCT04794699

Conditions

  • Solid Tumor

Interventions

DrugSynonymsArms
IDE397Dose Escalation Monotherapy

Purpose

This is a Phase 1, open-label, multicenter, multiple dose, dose escalation study of the safety, PK, PD, and anti-tumor activity of IDE397 as a single agent 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.

Trial Arms

NameTypeDescriptionInterventions
Dose Escalation MonotherapyExperimentalIDE397 dosed orally, once daily (QD) for each 21-day cycle
  • IDE397

Eligibility Criteria

        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 at the DNA or protein level
             in the participant's tumor tissue

          -  Measurable disease

          -  ECOG performance status <= 1 or 2

          -  Adequate organ function

          -  Able to swallow and retain orally administered study treatment

          -  Able to comply with contraceptive/barrier requirements

        Exclusion Criteria:

          -  Known symptomatic brain metastases that are not neurologically stable for 3 months

          -  Known primary CNS malignancy

          -  Current active liver or biliary disease

          -  Active inflammatory gastrointestinal disease, chronic diarrhea, known diverticular
             disease or previous gastric resection or lap band surgery

          -  Impairment of gastrointestinal (GI) function or GI disease that may significantly
             alter the absorption of IDE397

          -  Active, uncontrolled infection including hepatitis B virus, hepatitis C virus, human
             immunodeficiency virus, or acquired immunodeficiency syndrome related illness

          -  Baseline 12 lead ECG that demonstrates clinically relevant abnormalities

          -  Clinically significant cardiac events 6 months before study entry

          -  Uncontrolled hypertension despite optimal medical therapy

          -  Previous treatment with a MAT2A inhibitor and / or PRMT inhibitor

          -  Major surgery within 4 weeks prior to C1D1

          -  Radiation therapy within 4 weeks prior to C1D1

          -  Systemic anti-cancer therapy (non-monoclonal antibody) within 4 weeks prior to study
             entry or within 28 days prior to study entry for an antibody based agent(s) or 5
             half-lives (whichever is shorter)

          -  Have received radioimmunotherapy less than 6 weeks before the first dose of IDE397

          -  Have received treatment with a therapeutic antibody less than 4 weeks before the first
             dose of IDE397

          -  Have received treatment with an investigational small molecule less than 2 weeks
             before the first dose of IDE397

          -  Prior irradiation to >25% of the bone marrow

          -  Current use or anticipated need for food or drugs that are known strong CYP3A4/5
             inhibitors

          -  Current use or anticipated need for food or drugs that are known strong CYP3A4/5
             inducers

          -  Received an investigational product within 28 days prior to first dose of IDE-397 or 5
             half-lives (whichever is shorter)

          -  Exposure to more than 4 investigational medicinal products within 12 months prior to
             C1D1

          -  Known or suspected hypersensitivity to IDE397/excipients or components
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose-limiting Toxicities (DLTs) of IDE397
Time Frame:21 days following the first dose of IDE397
Safety Issue:
Description:Incidence of DLTs of IDE397 will be determined

Secondary Outcome Measures

Measure:Plasma Pharmacokinetics of IDE397 and metabolite
Time Frame:Approximately 2 years
Safety Issue:
Description:Pharmacokinetics of IDE397 and metabolite following single and multiple oral administration will be determined
Measure:Preliminary anti-tumor activity
Time Frame:Approximately 2 years
Safety Issue:
Description:Objective response rate and duration of response will be assessed using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Measure:Pharmacodynamic effect of IDE397
Time Frame:Approximately 2 years
Safety Issue:
Description:Changes in the levels of MAT2A pathway (SAM and MAT2A) and PRMT5 pathway (SDMA) will be determined

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:IDEAYA Biosciences

Trial Keywords

  • MAT2A
  • 9p21
  • CDKN2A
  • MTAP
  • Solid Tumors
  • PRMT5
  • SAM
  • Synthetic Lethality
  • Inhibitor
  • MTAP deletion
  • CDKN2A deletion
  • MAT2A Inhibitor
  • Advanced solid tumors
  • Lung Cancer
  • Pancreatic or Pancreas Cancer
  • Bladder Cancer
  • Renal Cancer
  • Mesothelioma
  • Esophageal Cancer
  • Head and Neck Squamous Cell Carcinoma
  • Gastric Cancer
  • Breast cancer
  • Melanoma
  • Cholangiocarcinoma

Last Updated

June 29, 2021