Clinical trial NCT04794699: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Keywords: MAT2A
9p21
CDKN2A
MTAP
Solid Tumors
PRMT5
SAM
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
Sacituzumab govitecan
Trodelvy
Lead sponsor: IDEAYA Biosciences
Sponsor class: INDUSTRY
First posted: 2021-03-12
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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
* 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 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

Primary outcomes:
measure: Dose-limiting Toxicities (DLTs) of IDE397
timeFrame: 21 days following the first dose of IDE397
measure: Dose-limiting Toxicities (DLTs) of IDE397 in combination with docetaxel or paclitaxel or sacituzumab govitecan
timeFrame: 21 - 28 days following the first dose of IDE397
measure: Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of IDE397
timeFrame: Approximately 2 years
measure: Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of IDE397 in combination with docetaxel or paclitaxel or sacituzumab govitecan
timeFrame: Approximately 2 years
measure: To evaluate preliminary anti-tumor activity of IDE397 in combination expansion arms
timeFrame: Approximately 2 years
Secondary outcomes:
measure: Plasma Pharmacokinetics of IDE397 and metabolite
timeFrame: Approximately 2 years
measure: Drug interaction between IDE397 and docetaxel or paclitaxel or sacituzumab govitecan
timeFrame: Approximately 2 years
measure: Pharmacodynamic effect of IDE397 as a single agent and in combination with docetaxel or paclitaxel or sacituzumab govitecan
timeFrame: Approximately 2 years
measure: Preliminary anti-tumor activity in IDE397 escalation and combination escalation arms
timeFrame: Approximately 2 years
Other outcomes:
Locations:
city: Scottsdale
country: United States
facility: Honor Health Research Institute
state: Arizona
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Duarte
country: United States
facility: City of Hope
state: California
city: Santa Rosa
country: United States
facility: Providence Medical Group
state: California
city: Celebration
country: United States
facility: Advent Health
state: Florida
city: Orlando
country: United States
facility: Orlando Health Cancer Institute
state: Florida
city: Indianapolis
country: United States
facility: Indiana University Health Hospital
state: Indiana
city: Lexington
country: United States
facility: Markey Cancer Center
state: Kentucky
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Barbara Ann Karmanos Cancer Institute
state: Michigan
city: New York
country: United States
facility: Columbia University Medical Center - Herbert Irving Pavilion
state: New York
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Oklahoma City
country: United States
facility: Stephenson Cancer Center
state: Oklahoma
city: Providence
country: United States
facility: LifeSpan - Brown University
state: Rhode Island
city: Nashville
country: United States
facility: SCRI Oncology Partners
state: Tennessee
city: Houston
country: United States
facility: MD Anderson
state: Texas
city: San Antonio
country: United States
facility: Next Oncology
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Darlinghurst
country: Australia
facility: The Kinghorn Cancer Centre, St Vincent's Health Network Sydney
state: New South Wales
city: Bedford Park
country: Australia
facility: Southern Oncology Clinical Research Unit
state: South Australia
city: Bordeaux
country: France
facility: Institut Bergonie
state: Bordeaux Cedex
city: Toulouse
country: France
facility: Institut Claudius Regaud - IUCT-Oncopole
state: Cedex 9
city: Marseille
country: France
facility: Hôpital Timone
city: Rennes
country: France
facility: Centre Eugène Marquis
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg-Eppendorf (UKE)
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
state: Chungcheongbuk-Do
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
state: Gyeonggi
city: Seongnam-si
country: Korea, Republic of
facility: CHA University - Bundang Medical Center
state: Gyeonggi
city: Seoul
country: Korea, Republic of
facility: Sevrance Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Barcelona
country: Spain
facility: Vall Hebron Institute of Oncology
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre (H12O)
city: Madrid
country: Spain
facility: START Madrid-HM - Centro Integral Oncológico Clara Campal (CIOCC)
city: Madrid
country: Spain
facility: NEXT Madrid, Universitary Hospital QuironSAlud
city: Valencia
country: Spain
facility: Instituto Valenciano de Oncología (IVO)
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: IDEAYA Biosciences
name: Jasgit Sachdev, MD
role: STUDY_DIRECTOR
References: