Study of IDE397 in Participants With Solid Tumors Harboring MTAP Deletion
- Conditions
- Solid Tumor
- Interventions
- Registration Number
- NCT04794699
- Lead Sponsor
- IDEAYA Biosciences
- Brief Summary
This is a Phase 1, open-label, multicenter, dose escalation and expansion study of the safety, PK, PD, and preliminary anti-tumor activity of IDE397 as a single agent and in combination with other anticancer agents including taxanes (docetaxel, paclitaxel), or sacituzumab govitecan (SG), in adult patients with selected advanced or metastatic MTAP-deleted advanced solid tumors who are unresponsive to standard of care therapy. IDE397 is a small molecule inhibitor of methionine adenosyltransferase 2 alpha (MAT2A).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 180
- 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
- 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 or sacituzumab govitecan
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Part 2: Monotherapy Dose Expansion (NSCLC, EG and Urothelial) IDE397 - Part 4: Combination Dose Expansion with docetaxel or paclitaxel (NSCLC, EG and Urothelial) Paclitaxel - Part 5: Combination Dose Escalation with sacituzumab govitecan (SG) (Urothelial) Sacituzumab govitecan - Part 6: Combination Dose Expansion with sacituzumab govitecan (SG) (Urothelial) IDE397 - Part 6: Combination Dose Expansion with sacituzumab govitecan (SG) (Urothelial) Sacituzumab govitecan - Part 3: Combination Dose Escalation with docetaxel or paclitaxel (NSCLC, EG and Urothelial) IDE397 - Part 3: Combination Dose Escalation with docetaxel or paclitaxel (NSCLC, EG and Urothelial) Paclitaxel - Part 5: Combination Dose Escalation with sacituzumab govitecan (SG) (Urothelial) IDE397 - Part 4: Combination Dose Expansion with docetaxel or paclitaxel (NSCLC, EG and Urothelial) IDE397 - Part 1: Dose Escalation Monotherapy (Solid Tumors) IDE397 - Part 3: Combination Dose Escalation with docetaxel or paclitaxel (NSCLC, EG and Urothelial) Docetaxel - Part 4: Combination Dose Expansion with docetaxel or paclitaxel (NSCLC, EG and Urothelial) Docetaxel -
- Primary Outcome Measures
Name Time Method To evaluate preliminary anti-tumor activity of IDE397 in combination expansion arms Approximately 2 years Objective Response Rate (ORR) and Duration of Response (DoR)
Dose-limiting Toxicities (DLTs) of IDE397 21 days following the first dose of IDE397 Incidence of DLTs of IDE397 will be determined
Dose-limiting Toxicities (DLTs) of IDE397 in combination with docetaxel or paclitaxel or sacituzumab govitecan 21 - 28 days following the first dose of IDE397 Incidence of DLTs of IDE397 in a combination setting will be determined
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of IDE397 Approximately 2 years MTD and RP2D of IDE397 will be determined
Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of IDE397 in combination with docetaxel or paclitaxel or sacituzumab govitecan Approximately 2 years MTD and RP2D of IDE397 in a combination setting will be determined
- Secondary Outcome Measures
Name Time Method Plasma Pharmacokinetics of IDE397 and metabolite Approximately 2 years Pharmacokinetics of IDE397 and metabolite following single and multiple oral administration as a single agent and in combination with docetaxel or paclitaxel or sacituzumab govitecan, will be determined
Pharmacodynamic effect of IDE397 as a single agent and in combination with docetaxel or paclitaxel or sacituzumab govitecan Approximately 2 years Changes in the levels of MAT2A pathway and PRMT5 pathway will be determined
Preliminary anti-tumor activity in IDE397 escalation and combination escalation arms Approximately 2 years Objective response rate and duration of response will be assessed by Investigator using the Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Drug interaction between IDE397 and docetaxel or paclitaxel or sacituzumab govitecan Approximately 2 years Pharmacokinetics of docetaxel or paclitaxel or sacituzumab govitecan.
Trial Locations
- Locations (38)
Honor Health Research Institute
🇺🇸Scottsdale, Arizona, United States
University of Arkansas for Medical Sciences
🇺🇸Little Rock, Arkansas, United States
City of Hope
🇺🇸Duarte, California, United States
Providence Medical Group
🇺🇸Santa Rosa, California, United States
Advent Health
🇺🇸Celebration, Florida, United States
Orlando Health Cancer Institute
🇺🇸Orlando, Florida, United States
Indiana University Health Hospital
🇺🇸Indianapolis, Indiana, United States
Markey Cancer Center
🇺🇸Lexington, Kentucky, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Scroll for more (28 remaining)Honor Health Research Institute🇺🇸Scottsdale, Arizona, United States