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.
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
Interventions
Drug | Synonyms | Arms |
---|
IDE397 | | Dose 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
Name | Type | Description | Interventions |
---|
Dose Escalation Monotherapy | Experimental | IDE397 dosed orally, once daily (QD) for each 21-day cycle | |
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
August 26, 2021