A Study Evaluating AMG 193 in Combination With Other Therapies in Participants With Advanced Gastrointestinal, Biliary Tract, or Pancreatic Cancers With Homozygous Methylthioadenosine Phosphorylase (MTAP)-Deletion (MTAPESTRY 103)

NCT ID: NCT06360354

Last Updated: 2026-01-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

350 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-05-29

Study Completion Date

2029-02-25

Brief Summary

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The study aims to determine maximum tolerated dose (MTD) or recommended combination dose of the MTA-cooperative PRMT5 inhibitor AMG 193 administered in combination with other therapies in adult participants with metastatic or locally advanced methylthioadenosine phosphorylase (MTAP)-deleted gastrointestinal, biliary tract, or pancreatic cancers. The study also aims to determine the safety profile of AMG 193 administered in combination with other therapies in adult participants with metastatic or locally advanced MTAP-deleted gastrointestinal, biliary tract, or pancreatic cancers.

Detailed Description

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Conditions

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Advanced Gastrointestinal, Biliary Tract, and Pancreatic Cancers

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Subprotocol C: Dose Exploration

Part 1: Participants with MTAP-deleted PDAC will receive oral doses of AMG 193 and RMC-6236.

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

Administered Orally

RMC-6236

Intervention Type DRUG

Administered orally

Subprotocol C: Dose Expansion

Part 2: Participants with MTAP-deleted PDAC will receive oral doses of AMG 193 andRMC-6236.

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

Administered Orally

RMC-6236

Intervention Type DRUG

Administered orally

Subprotocol B: Pancreatic Ductal Adenocarcinoma (PDAC) Arm A

Part 1: Participants with MTAP-deleted PDAC will receive doses of AMG 193 orally in combination with gemcitabine and nab-paclitaxel IV.

Part 2: Participants with MTAP-deleted PDAC will receive the recommended dose of AMG 193 in combination with gemcitabine and nab-paclitaxel.

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

Administered Orally

Gemcitabine

Intervention Type DRUG

Administered IV

Nab-paclitaxel

Intervention Type DRUG

Administered IV

Subprotocol B: PDAC Arm B

Part 1: Participants with MTAP-deleted PDAC will receive doses of AMG 193 orally in combination with mFOLFIRINOX (irinotecan, fluorouracil, leucovorin calcium, oxaliplatin) IV.

Part 2: Participants with MTAP-deleted PDAC will receive the recommended dose of AMG 193 in combination with mFOLFIRINOX.

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

Administered Orally

Modified FOLFIRINOX

Intervention Type DRUG

Modified FOLFIRINOX consists of irinotecan, 5-FU, LV, and oxaliplatin administered IV

Interventions

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AMG 193

Administered Orally

Intervention Type DRUG

Gemcitabine

Administered IV

Intervention Type DRUG

Nab-paclitaxel

Administered IV

Intervention Type DRUG

Modified FOLFIRINOX

Modified FOLFIRINOX consists of irinotecan, 5-FU, LV, and oxaliplatin administered IV

Intervention Type DRUG

RMC-6236

Administered orally

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years).
* Histologically or cytologically confirmed diagnosis of metastatic and/or unresectable (locally advanced) adenocarcinoma of the pancreas.
* Tumor tissue (FFPE sample) or an archival block must be available. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before dosing.
* Homozygous MTAP-deletion.
* Disease measurable as defined by RECIST v1.1.
* Adequate organ function as defined in the protocol.

Exclusion:

* Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor.
* Radiation therapy within 28 days of first dose.
* Major surgery within 28 days of first dose of AMG 193.

Exclusion Criteria

* Gastrointestinal tract disease causing the inability to take PO medication, malabsorption syndrome, requirement for IV alimentation, gastric/jejunal tube feeds, uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative colitis).
* History of solid organ transplantation.

Subprotocol C

Inclusion:

* Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years).
* Histologically or cytologically confirmed diagnosis of metastatic and/or unresectable (locally advanced) adenocarcinoma of the pancreas.
* Homozygous MTAP-deletion.
* Rat Sarcoma Viral Oncogene Homolog (RAS) mutation
* Received at least 1 prior systemic therapy for advanced or metastatic PDAC.
* Disease measurable as defined by RECIST v1.1.
* Adequate organ function as defined in the protocol.

Exclusion:

* Prior treatment with aMAT2A inhibitor, a PRMT5 inhibitor, or a MAPK pathway inhibitor, including KRAS inhibitors.
* Gastrointestinal tract disease causing the inability to take PO medication, malabsorption syndrome, requirement for IV alimentation, gastric/jejunal tube feeds, uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative colitis).
* History of solid organ transplantation.
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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Comprehensive Blood and Cancer Center

Bakersfield, California, United States

Site Status RECRUITING

City of Hope National Medical Center

Duarte, California, United States

Site Status RECRUITING

City of Hope Orange County Lennar Foundation Cancer Center

Duarte, California, United States

Site Status RECRUITING

University of California San Diego Moores Cancer Center

La Jolla, California, United States

Site Status RECRUITING

Translational Research in Oncology US Inc, Trio Central Pharmacy

Los Angeles, California, United States

Site Status RECRUITING

University of California Los Angeles

Santa Monica, California, United States

Site Status RECRUITING

Rocky Mountain Cancer Centers

Aurora, Colorado, United States

Site Status RECRUITING

Hartford Hospital

Hartford, Connecticut, United States

Site Status RECRUITING

Yale University

New Haven, Connecticut, United States

Site Status RECRUITING

Norwalk Hospital

Norwalk, Connecticut, United States

Site Status RECRUITING

University of Chicago

Chicago, Illinois, United States

Site Status RECRUITING

Indiana University

Indianapolis, Indiana, United States

Site Status RECRUITING

Norton Cancer Institute

Louisville, Kentucky, United States

Site Status RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Washington University

St Louis, Missouri, United States

Site Status RECRUITING

University of Nebraska

Omaha, Nebraska, United States

Site Status RECRUITING

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status TERMINATED

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Duke University

Durham, North Carolina, United States

Site Status RECRUITING

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status RECRUITING

United States Oncology Regulatory Affairs Corporate Office

Nashville, Tennessee, United States

Site Status RECRUITING

Oncology Consultants Cancer Center

Houston, Texas, United States

Site Status TERMINATED

US Oncology Research Investigational Products Center

Irving, Texas, United States

Site Status RECRUITING

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Site Status RECRUITING

Virginia Cancer Specialists PC

Fairfax, Virginia, United States

Site Status RECRUITING

Fred Hutchinson Cancer Center

Seattle, Washington, United States

Site Status RECRUITING

Northwest Medical Specialties, PLLC

Tacoma, Washington, United States

Site Status RECRUITING

Northwest Cancer Specialists - Vancouver

Vancouver, Washington, United States

Site Status RECRUITING

Chris OBrien Lifehouse

Camperdown, New South Wales, Australia

Site Status RECRUITING

GenesisCare -North Shore Oncology

St Leonards, New South Wales, Australia

Site Status RECRUITING

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Site Status RECRUITING

Austin Health, Austin Hospital

Heidelberg, Victoria, Australia

Site Status RECRUITING

Peter MacCallum Cancer Centre

Melbourne, Victoria, Australia

Site Status RECRUITING

Epworth Healthcare

St Albans, Victoria, Australia

Site Status RECRUITING

Universite Catholique de Louvain Cliniques Universitaires Saint Luc

Brussels, , Belgium

Site Status RECRUITING

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Site Status RECRUITING

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, , Belgium

Site Status RECRUITING

Arthur J E Child Comprehensive Cancer Centre

Calgary, Alberta, Canada

Site Status RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status RECRUITING

CHU de Quebec Hopital de l Enfant Jesus

Québec, Quebec, Canada

Site Status RECRUITING

Mengchao Hepatobiliary Hospital of Fujian Medical University

Fuzhou, Fujian, China

Site Status RECRUITING

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, China

Site Status RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, China

Site Status RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, China

Site Status RECRUITING

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, China

Site Status RECRUITING

The First Bethune Hospital of Jilin University

Changchun, Jilin, China

Site Status RECRUITING

Herlev og Gentofte Hospital

Herlev, , Denmark

Site Status RECRUITING

Institut Bergonie

Bordeaux, , France

Site Status RECRUITING

Centre Georges Francois Leclerc

Dijon, , France

Site Status RECRUITING

Institut Paoli Calmettes

Marseille, , France

Site Status RECRUITING

Gustave Roussy

Villejuif, , France

Site Status RECRUITING

Universitaetsklinikum Essen

Essen, , Germany

Site Status RECRUITING

Universitaetsklinikum Heidelberg

Heidelberg, , Germany

Site Status RECRUITING

Universitaetsklinikum Wuerzburg

Würzburg, , Germany

Site Status RECRUITING

Alexandra Hospital

Athens, , Greece

Site Status RECRUITING

General Hospital Of Thessaloniki Papageorgiou

Thessaloniki, , Greece

Site Status RECRUITING

European Interbalkan Medical Center

Thessaloniki, , Greece

Site Status RECRUITING

Queen Mary Hospital, The University of Hong Kong

Hong Kong, , Hong Kong

Site Status RECRUITING

Prince of Wales Hospital, Chinese University of Hong Kong

Shatin, New Territories, , Hong Kong

Site Status RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Site Status RECRUITING

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, , Italy

Site Status RECRUITING

IRCCS Istituto Clinico Humanitas

Rozzano MI, , Italy

Site Status RECRUITING

Centro Ricerche Cliniche Di Verona Societa responsabilita limitata

Verona, , Italy

Site Status RECRUITING

Aichi Cancer Center

Nagoya, Aichi-ken, Japan

Site Status RECRUITING

National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan

Site Status RECRUITING

Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center

Yokohama, Kanagawa, Japan

Site Status RECRUITING

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Site Status RECRUITING

Radboud Universitair Medisch Centrum

Nijmegen, , Netherlands

Site Status RECRUITING

Hospital Universitario Virgen del Rocio

Seville, Andalusia, Spain

Site Status RECRUITING

Hospital Universitari Vall d Hebron

Barcelona, Catalonia, Spain

Site Status RECRUITING

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Site Status RECRUITING

National Cheng Kung University Hospital

Tainan, , Taiwan

Site Status RECRUITING

National Taiwan University Hospital

Taipei, , Taiwan

Site Status RECRUITING

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status RECRUITING

Queen Elizabeth Hospital Birmingham

Birmingham, , United Kingdom

Site Status RECRUITING

Sarah Cannon Research Institute UK

London, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Belgium Canada China Denmark France Germany Greece Hong Kong Italy Japan Netherlands Spain Taiwan United Kingdom

Central Contacts

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Amgen Call Center

Role: CONTACT

866-572-6436

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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20230223

Identifier Type: -

Identifier Source: org_study_id

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