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 Drug interaction between IDE397 and docetaxel or paclitaxel or sacituzumab govitecan Approximately 2 years Pharmacokinetics of docetaxel or paclitaxel or sacituzumab govitecan.
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)
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
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
Columbia University Medical Center - Herbert Irving Pavilion
🇺🇸New York, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Stephenson Cancer Center
🇺🇸Oklahoma City, Oklahoma, United States
LifeSpan - Brown University
🇺🇸Providence, Rhode Island, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
MD Anderson
🇺🇸Houston, Texas, United States
Next Oncology
🇺🇸San Antonio, Texas, United States
Swedish Cancer Institute
🇺🇸Seattle, Washington, United States
The Kinghorn Cancer Centre, St Vincent's Health Network Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Southern Oncology Clinical Research Unit
🇦🇺Bedford Park, South Australia, Australia
Institut Bergonie
🇫🇷Bordeaux, Bordeaux Cedex, France
Institut Claudius Regaud - IUCT-Oncopole
🇫🇷Toulouse, Cedex 9, France
Hôpital Timone
🇫🇷Marseille, France
Centre Eugène Marquis
🇫🇷Rennes, France
Universitaetsklinikum Hamburg-Eppendorf (UKE)
🇩🇪Hamburg, Germany
Chungbuk National University Hospital
🇰🇷Cheongju-si, Chungcheongbuk-Do, Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Gyeonggi, Korea, Republic of
CHA University - Bundang Medical Center
🇰🇷Seongnam-si, Gyeonggi, Korea, Republic of
Sevrance Hospital
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Vall Hebron Institute of Oncology
🇪🇸Barcelona, Spain
Hospital Universitario 12 de Octubre (H12O)
🇪🇸Madrid, Spain
START Madrid-HM - Centro Integral Oncológico Clara Campal (CIOCC)
🇪🇸Madrid, Spain
NEXT Madrid, Universitary Hospital QuironSAlud
🇪🇸Madrid, Spain
Instituto Valenciano de Oncología (IVO)
🇪🇸Valencia, Spain
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan