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MTAP欠損進行固形腫瘍におけるIDE892の単剤療法および併用療法に関する研究

2026年9月24日 更新者：IDEAYA Biosciences

MTAP欠損進行性固形腫瘍患者におけるIDE892の単剤療法および併用療法の安全性、有効性、薬物動態を評価する多施設共同研究

This is a multicenter clinical study to evaluate the safety, efficacy, and Pharmacokinetics (PK) of IDE892 as monotherapy and in combination with other agents including IDE397 in participants with methylthioadenosine phosphorylase (MTAP)-deleted advanced solid tumors within indications of interest.

調査の概要

状態

募集

条件

介入・治療

詳細な説明

The purpose of this study is to evaluate safety, efficacy, and PK of IDE892 as monotherapy and combination therapy in adult participants with MTAP-deleted tumors who have progressed after standard therapy and represent a high unmet need. In the current stage, the combination will be focused on IDE892 with IDE397, an oral inhibitor of methionine adenosyltransferase 2A (MAT2A), to fully exploit the vulnerabilities associated with methylthioadenosine (MTA) accumulation in MTAP-deleted tumors while maintaining a substantial therapeutic index. The mechanistic rationale for this study is discussed in the following sections.

研究の種類

介入

入学 (推定)

260

段階

  • フェーズ 1

連絡先と場所

このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。

研究連絡先

研究場所

  • アメリカ
    • Arizona
      • Goodyear、Arizona、アメリカ、85338
        • 募集
        • City of Hope Cancer Center-Phoenix
        • コンタクト：
      • Phoenix、Arizona、アメリカ、85054
        • 募集
        • Mayo Clinic Arizona
        • コンタクト：
          • Mitesh J. Borad, M.D.
          • 電話番号：855-776-0015
    • California
      • Duarte、California、アメリカ、91010
        • 募集
        • City of Hope Cancer Center-Duarte
        • コンタクト：
      • Santa Rosa、California、アメリカ、95403
        • 募集
        • Providence Medical Foundation
        • コンタクト：
    • District of Columbia
      • Washington D.C.、District of Columbia、アメリカ、20016
    • Florida
      • Coral Springs、Florida、アメリカ、33065
        • 募集
        • BRCR Global-Coral Springs
        • コンタクト：
      • Jacksonville、Florida、アメリカ、32224
        • 募集
        • Mayo Clinic Florida
        • コンタクト：
          • Conor D. O'Donnell, M.B., B.Ch., B.A.O.
          • 電話番号：855-776-0015
      • Orlando、Florida、アメリカ、32827
        • 募集
        • Sarah Cannon Research Institute at Florida Cancer Specialists
        • コンタクト：
      • Tampa、Florida、アメリカ、33612
    • Illinois
      • Zion、Illinois、アメリカ、60099
        • 募集
        • City of Hope Cancer Center-Chicago
        • コンタクト：
          • Evan Pisick, M.D.
          • 電話番号：415-353-9674
          • メール：episick@coh.org
    • Minnesota
      • Rochester、Minnesota、アメリカ、55905
        • 募集
        • Mayo Clinic Rochester
        • コンタクト：
          • Kaushal Parikh, M.B.B.S.
          • 電話番号：855-776-0015
    • Nebraska
      • Omaha、Nebraska、アメリカ、68130
        • 募集
        • Nebraska Cancer Specialists
        • コンタクト：
    • New Jersey
      • East Brunswick、New Jersey、アメリカ、08816
    • New York
      • New York、New York、アメリカ、10032
        • 募集
        • Columbia University Irving Medical Center
        • コンタクト：
    • Pennsylvania
      • Philadelphia、Pennsylvania、アメリカ、19107
        • 募集
        • Sidney Kimmel Comprehensive Cancer Center Thomas Jefferson University
        • コンタクト：
        • コンタクト：
          • askphase1@jefferson.edu
          • 電話番号：215-586-0199
    • Tennessee
      • Nashville、Tennessee、アメリカ、37203
        • 募集
        • Sarah Cannon Research Institute
        • コンタクト：
        • コンタクト：
    • Texas
      • Fort Worth、Texas、アメリカ、76104
      • Houston、Texas、アメリカ、77030
        • 募集
        • MD Anderson
        • コンタクト：
      • Houston、Texas、アメリカ、77054
        • 募集
        • NEXT Oncology Houston
        • コンタクト：
      • Irving、Texas、アメリカ、75039
        • 募集
        • NEXT Oncology Dallas
        • コンタクト：
    • Utah
      • West Valley City、Utah、アメリカ、84119
        • 募集
        • START Mountain Region, LLC
        • コンタクト：
    • Virginia
      • Fairfax、Virginia、アメリカ、22031
        • 募集
        • NEXT Oncology Virginia
        • コンタクト：
    • Washington
      • Seattle、Washington、アメリカ、98104

参加基準

研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。

適格基準

就学可能な年齢

18年歳以上 (大人、高齢者)

健康ボランティアの受け入れ

いいえ

受講資格のある性別

全て

説明

Inclusion Criteria:

  • Are ≥ 18 years of age (or the minimum age of consent in accordance with local regulations) at the time of signing the ICF.
  • Have a histologically confirmed diagnosis of a locally advanced recurrent or metastatic solid tumor type of interest with MTAP deletion (for dose escalation: mesothelioma [pleural or peritoneal], gastroesophageal cancers [squamous and adenocarcinoma of esophagus, gastric adenocarcinoma, gastroesophageal junction cancers], pancreatic adenocarcinoma and biliary tract carcinomas (intrahepatic and extrahepatic cholangiocarcinoma, and gallbladder cancer), NSCLC [adenocarcinoma, squamous cell carcinoma, and adeno-squamous] or UC [including mixed urothelial-squamous histology]; for dose expansion: NSCLC that has progressed on at least one prior line of treatment and for which additional effective standard therapy is not available or for which the participant is not a candidate due to intolerance).
  • Are willing and able to provide blood/tumor tissue samples for biomarker testing. An archival tumor tissue specimen must be provided for central confirmation of MTAP loss.
  • Must be willing and able to provide the blood/serum/plasma samples
  • Have evidence of homozygous loss of MTAP or MTAP deletion (pre-screening available after signing pre-screening ICF)
  • Have at least 1 measurable lesion according to RECIST version 1.1
  • Have Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1
  • Have life expectancy > 3 months
  • Have adequate bone marrow and organ function
  • Able to swallow and retain orally administered study drug/IMP.
  • Are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures
  • Male and female: willing to use contraception

Exclusion Criteria:

  • Known symptomatic brain metastases requiring supraphysiologic doses of systemic corticosteroids
  • Have a known primary central nervous system (CNS) malignancy
  • Have had other malignancies within 2 years prior to the first dose, with some exceptions
  • Impaired cardiac function or clinically significant cardiac diseases
  • Have presence of uncontrolled pleural, peritoneal, or pericardial effusion within 2 weeks before the first study dose, requiring recurrent drainage procedures or an indwelling drainage catheter
  • Have a history of severe infections within 4 weeks prior to the start of study treatment
  • Hypertension (e.g., > 150/100 mmHg) that cannot be controlled by medications despite optimal medical therapy
  • Other acute or chronic medical or psychiatric condition
  • Have a history of immunodeficiency, with a positive human immunodeficiency virus(HIV) test at screening
  • Known or suspected viral hepatitis with a positive test at screening
  • Had an adverse reaction to a previous antitumor treatment that has not recovered to CTCAE Grade ≤ 1
  • Have received chemotherapy within 4 weeks of the first dose of IMP; immunotherapy or biologic targeted antitumor treatments within 2 weeks before the first dose of IMP; small molecule inhibitors within 2 weeks before the first dose of IMP, or other investigational products within 4 weeks
  • Current radiation-related toxicity or radiation therapy within 2 weeks before the first dose of IMP
  • Administration of any of the following within 2 weeks before the first dose of IDE892 as a monotherapy: Strong inhibitors or inducers of cytochrome P450, Strong inhibitors of P-glycoprotein, Narrow therapeutic index and sensitive substrates of multidrug and toxin extrusion (MATE)1 and MATE2-K, Narrow therapeutic index and sensitive substrates of P-gp and breast cancer resistance protein
  • Administration of any of the following within 2 weeks before the first dose of IDE892: Strong inhibitors or inducers of CYP3A4/5, Strong inhibitors of P-gp and/or BCRP, Narrow therapeutic index and sensitive substrates of MATE1 and MATE2-K, Narrow therapeutic index and sensitive substrates of P-gp and BCRP
  • Use of proton pump inhibitors (PPIs) within 7 days prior to the first dose of IMP or planned use during the study
  • Use of drugs with known risk for QT prolongation within 2 weeks prior to the first dose of IDE892
  • Previous treatment with a Amethionine adenosyltransferase 2A (MAT2A) inhibitor and/or Protein arginine N-methyltransferase (PRMT) inhibitor
  • Major surgery within 4 weeks before study entry
  • Prior irradiation to > 25% of the bone marrow
  • Known or suspected hypersensitivity to IDE892

Disease-Specific Eligibility Criteria Eligibility Criteria for Participants with NSCLC (All Parts)

  • Must have histologically confirmed diagnosis of advanced or metastatic NSCLC that has progressed after prior treatment with platinum chemotherapy and a PD-1/PD-L1 inhibitor (unless contraindicated or participant developed intolerance) in the metastatic setting
  • Treatment with no more than 3 prior lines in the setting of advanced or metastatic disease.
  • If considered standard of care and available, participants whose cancers have proven targetable oncogene alterations must have had disease progression on (unless contraindicated or participant developed intolerance) at least 1 prior line containing appropriate targeted therapy.

Eligibility Criteria for Participants with Urothelial Cancer (Bladder and Upper Urinary Tract), Mesothelioma (Pleural or Peritoneal), Pancreatic Adenocarcinoma or Biliary Tract Carcinomas (Intrahepatic and Extrahepatic Cholangiocarcinoma, and Gallbladder Cancer) (Parts 1 and 3)

  • Must have histologically confirmed diagnosis of advanced or metastatic UC, mesothelioma, gastroesophageal cancer or pancreatic and biliary tract tumors
  • Must have progressed following at least 1 prior line of therapy
  • Treatment with no more than 3 prior lines in the setting of advanced or metastatic disease

研究計画

このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。

研究はどのように設計されていますか？

デザインの詳細

  • 主な目的：処理
  • 割り当て：非ランダム化
  • 介入モデル：順次割り当て
  • マスキング：なし（オープンラベル）

武器と介入

参加者グループ / アーム
介入・治療
実験的：Part 1: IDE892 Monotherapy Dose Escalation (MTAP-deleted advanced solid tumors)

Participants with advanced or metastatic solid tumors harboring MTAP deletion (including mesothelioma, gastroesophageal cancers, pancreatic and biliary tract tumors, non-small cell lung cancer, and urothelial cancer) will receive IDE892. Dose levels will be escalated sequentially using a Bayesian Optimal Interval (BOIN) design to evaluate safety, tolerability, and to determine the maximum tolerated dose and/or recommended dose for expansion. PK and pharmacodynamics (PD) and preliminary antitumor activity will also be assessed.
薬：IDE892

IDE892 is an inhibitor of the Protein arginine methyltransferase 5 (PRMT5) that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions.
実験的：Part 2: IDE892 Monotherapy Dose Expansion (MTAP-Deleted NSCLC)

Participants with advanced or metastatic NSCLC with MTAP deletion will receive IDE892. One or more dose levels at or below the maximum tolerated dose from Part 1 will be further evaluated to determine the recommended Phase 2 dose and to assess antitumor activity.
薬：IDE892

IDE892 is an inhibitor of the Protein arginine methyltransferase 5 (PRMT5) that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions.
実験的：Part 3: IDE892 + IDE397 Combination Dose Escalation (MTAP-Deleted Solid Tumors)

Participants with advanced or metastatic solid tumors harboring MTAP deletion (including mesothelioma, gastroesophageal cancers, pancreatic and biliary tract tumors, non-small cell lung cancer, and urothelial cancer) will receive IDE892 in combination with IDE397. Dose levels will be escalated using a modified toxicity probability interval (mTPI) design to evaluate safety, tolerability, and to determine the maximum tolerated dose and/or recommended dose for expansion. PK, PD, and preliminary antitumor activity will also be assessed.
薬：IDE892

IDE892 is an inhibitor of the Protein arginine methyltransferase 5 (PRMT5) that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions.

薬：IDE397

IDE397 is an oral MAT2A inhibitor that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions. In this study, IDE397 will be evaluated in combination with IDE892 (Parts 3 and 4) in participants with MTAP-deleted advanced solid tumors.
実験的：Part 4: IDE892 + IDE397 Combination Dose Expansion (MTAP-Deleted NSCLC)

Participants with advanced or metastatic NSCLC with MTAP deletion will receive IDE892 in combination with IDE397. One or more dose levels at or below the maximum tolerated dose from Part 3 will be further evaluated to determine the recommended Phase 2 dose and to assess antitumor activity.
薬：IDE892

IDE892 is an inhibitor of the Protein arginine methyltransferase 5 (PRMT5) that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions.

薬：IDE397

IDE397 is an oral MAT2A inhibitor that is being developed by IDEAYA Biosciences, Inc. as an anticancer therapeutic for patients with advanced or metastatic cancer harboring MTAP deletions. In this study, IDE397 will be evaluated in combination with IDE892 (Parts 3 and 4) in participants with MTAP-deleted advanced solid tumors.

この研究は何を測定していますか？

主要な結果の測定

結果測定
メジャーの説明
時間枠
Incidence of Dose-limiting Toxicities (DLTs) of IDE892 (Parts 1 and 3)
時間枠：21 days following the first dose of IDE892 (each cycle is 21 days)

Incidence of DLTs of IDE892 will be determined in Parts 1 and 3
21 days following the first dose of IDE892 (each cycle is 21 days)
Incidence of AEs and SAEs (Parts 1, 2, 3, and 4)
時間枠：From first dose until 28 days after last dose (each cycle is 21 days)

Incidence and severity of adverse events (AEs)/serious adverse events (SAEs) (graded based on Common Terminology Criteria for Adverse Events [CTCAE] version 5.0) will be determined in Parts 1, 2, 3, and 4.
From first dose until 28 days after last dose (each cycle is 21 days)
Objective response rate (ORR) and duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (Parts 2 and 4)
時間枠：Approximately 2 years

Objective response rate (ORR: best objective response of complete response [CR] + partial response [PR]) and duration of response (DOR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as assessed by the Investigator
Approximately 2 years

二次結果の測定

結果測定
メジャーの説明
時間枠
Overall response rate (ORR) and duration of response (DOR) per RECIST version 1.1 (Parts 1 and 3)
時間枠：Approximately 2 years

ORR and DOR per RECIST version 1.1 as assessed by the Investigator
Approximately 2 years
Disease control rate (DCR) and duration of stable disease per RECIST version 1.1 (Parts 1, 2, 3, and 4)
時間枠：Approximately 2 years

Disease control rate (disease control rate [DCR]: CR + PR + stable disease [SD]) and duration of SD per RECIST version 1.1 as assessed by the Investigator
Approximately 2 years
Maximum Observed Plasma Concentration (Cmax) (Parts 1, 2, 3, and 4)
時間枠：Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

Cmax is the highest observed plasma concentration of the study drug following administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Time to Maximum Observed Concentration (Tmax)
時間枠：Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

Time to Maximum Observed Concentration (Tmax) after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast)
時間枠：Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

AUClast reflects total drug exposure from dosing until the last measurable concentration after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Time of Last Quantifiable Concentration (Tlast)
時間枠：Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

Tlast is the time at which the final measurable drug concentration is observed after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf)
時間枠：Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

AUCinf represents total drug exposure extrapolated to infinite time after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Terminal Elimination Half-Life (t½)
時間枠：Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

t½ is the time required for the plasma concentration of the drug to decrease by half during the terminal elimination phase after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Maximum Observed Plasma Concentration at Steady State (Cmax,ss)
時間枠：Cycle 1 Day 15 (each cycle is 21 days)

Cmax,ss is the maximum observed plasma concentration after achieving steady state after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 15 (each cycle is 21 days)
Time to Maximum Concentration at Steady State (Tmax,ss)
時間枠：Cycle 1 Day 15 (each cycle is 21 days)

Tmax,ss is the time from dosing to Cmax at steady state after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 15 (each cycle is 21 days)
Trough Plasma Concentration at Steady State (Ctrough)
時間枠：Cycle 1 Day 15 (each cycle is 21 days)

Ctrough is the concentration obtained immediately prior to the next scheduled dose at steady state after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 15 (each cycle is 21 days)
Area Under the Plasma Concentration-Time Curve Over the Dosing Interval (AUCtau)
時間枠：Cycle 1 Day 15 (each cycle is 21 days)

AUCtau represents drug exposure over one full dosing interval at steady state after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 15 (each cycle is 21 days)
Apparent Clearance (CL/F)
時間枠：Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

CL/F is the apparent clearance of the drug after extravascular dosing after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Apparent Volume of Distribution (Vz/F)
時間枠：Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

Vz/F is the apparent volume of distribution following extravascular dosing after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)
Accumulation Ratio (Rac)
時間枠：Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

Rac is calculated as the ratio of AUC or Cmax at steady state compared with first dose, reflecting drug accumulation after administration of IDE892 as a single agent or in combination with IDE397
Cycle 1 Day 1 and Cycle 1 Day 15 (each cycle is 21 days)

協力者と研究者

ここでは、この調査に関係する人々や組織を見つけることができます。

スポンサー

IDEAYA Biosciences

捜査官

  • スタディディレクター：Edward Chan, MD、IDEAYA Biosciences

研究記録日

これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。

主要日程の研究

研究開始 (実際)

2026年3月4日

一次修了 (推定)

2028年4月30日

研究の完了 (推定)

2028年4月30日

試験登録日

最初に提出

2025年11月13日

QC基準を満たした最初の提出物

2025年12月9日

最初の投稿 (実際)

2025年12月11日

学習記録の更新

投稿された最後の更新 (実際)

2026年9月28日

QC基準を満たした最後の更新が送信されました

2026年9月24日

最終確認日

2026年9月1日

詳しくは

本研究に関する用語

キーワード

追加の関連 MeSH 用語

その他の研究ID番号

  • IDE892-001

医薬品およびデバイス情報、研究文書

米国FDA規制医薬品の研究

はい

米国FDA規制機器製品の研究

いいえ

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