A Study Evaluating Anvumetostat in Combination With Other Therapies in Participants With Advanced Gastrointestinal, Biliary Tract, or Pancreatic Cancers With Homozygous Methylthioadenosine Phosphorylase (MTAP)-Deletion (MTAPESTRY 103)
MTAPESTRY 103
A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Anvumetostat in Combination With Other Therapies in Subjects With Advanced Gastrointestinal, Biliary Tract, or Pancreatic Cancers With Homozygous MTAP-deletion
1 other identifier
interventional
350
16 countries
77
Brief Summary
The study aims to determine maximum tolerated dose (MTD) or recommended combination dose of the MTA-cooperative PRMT5 inhibitor Anvumetostat 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 Anvumetostat administered in combination with other therapies in adult participants with metastatic or locally advanced MTAP-deleted gastrointestinal, biliary tract, or pancreatic cancers.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started May 2024
Longer than P75 for phase_1
77 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
April 8, 2024
CompletedFirst Posted
Study publicly available on registry
April 11, 2024
CompletedStudy Start
First participant enrolled
May 29, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 26, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
February 25, 2029
March 31, 2026
March 1, 2026
2.7 years
April 8, 2024
March 26, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Number of Participants Experiencing Dose Limiting Toxicities (DLT)
Up to 28 days
Number of Participants Experiencing Treatment Emergent Adverse Events (TEAE)
Any clinically significant changes in vital signs, electrocardiogram, or lab parameters will be recorded as TEAEs.
Up to approximately 2 years
Number of Participants Experiencing Serious Adverse Events (SAE)
Up to approximately 2 years
Secondary Outcomes (12)
Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Up to approximately 2 years
Disease Control (DC) per RECIST v1.1
Up to approximately 2 years
Duration of Response (DOR) per RECIST v1.1
Up to approximately 2 years
Time to Response (TTR) per RECIST v1.1
Up to approximately 2 years
Overall Survival (OS) per RECIST v1.1
Up to approximately 2 years
- +7 more secondary outcomes
Study Arms (4)
Subprotocol B: Pancreatic Ductal Adenocarcinoma (PDAC) Arm A
EXPERIMENTALPart 1: Participants with MTAP-deleted PDAC will receive doses of Anvumetostat orally in combination with gemcitabine and nab-paclitaxel IV. Part 2: Participants with MTAP-deleted PDAC will receive the recommended dose of Anvumetostat in combination with gemcitabine and nab-paclitaxel.
Subprotocol B: PDAC Arm B
EXPERIMENTALPart 1: Participants with MTAP-deleted PDAC will receive doses of Anvumetostat orally in combination with mFOLFIRINOX (irinotecan, fluorouracil, leucovorin calcium, oxaliplatin) IV. Part 2: Participants with MTAP-deleted PDAC will receive the recommended dose of Anvumetostat in combination with mFOLFIRINOX.
Subprotocol C: Dose Exploration
EXPERIMENTALPart 1: Participants with MTAP-deleted PDAC will receive oral doses of Anvumetostat and RMC-6236.
Subprotocol C: Dose Expansion
EXPERIMENTALPart 2: Participants with MTAP-deleted PDAC will receive oral doses of Anvumetostat andRMC-6236.
Interventions
Modified FOLFIRINOX consists of irinotecan, 5-FU, LV, and oxaliplatin administered IV
Administered Orally
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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 Anvumetostat.
- 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
- 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.
- 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).
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Amgenlead
Study Sites (77)
Comprehensive Blood and Cancer Center
Bakersfield, California, 93309, United States
City of Hope National Medical Center
Duarte, California, 91010, United States
City of Hope Orange County Lennar Foundation Cancer Center
Duarte, California, 91010, United States
University of California San Diego Moores Cancer Center
La Jolla, California, 92093, United States
Translational Research in Oncology US Inc, Trio Central Pharmacy
Los Angeles, California, 90095, United States
University of California Los Angeles
Santa Monica, California, 90404, United States
Rocky Mountain Cancer Centers
Aurora, Colorado, 80012, United States
Hartford Hospital
Hartford, Connecticut, 06106, United States
Yale University
New Haven, Connecticut, 06520, United States
Norwalk Hospital
Norwalk, Connecticut, 06856, United States
University of Chicago
Chicago, Illinois, 60637, United States
Indiana University
Indianapolis, Indiana, 46202, United States
Norton Cancer Institute
Louisville, Kentucky, 40202, United States
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Washington University
St Louis, Missouri, 63110, United States
University of Nebraska
Omaha, Nebraska, 68198, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10065, United States
Duke University
Durham, North Carolina, 27710, United States
Cleveland Clinic Foundation
Cleveland, Ohio, 44195, United States
United States Oncology Regulatory Affairs Corporate Office
Nashville, Tennessee, 37203, United States
Oncology Consultants Cancer Center
Houston, Texas, 77030, United States
US Oncology Research Investigational Products Center
Irving, Texas, 75063, United States
University of Virginia Cancer Center
Charlottesville, Virginia, 22903, United States
Virginia Cancer Specialists PC
Fairfax, Virginia, 22031, United States
Fred Hutchinson Cancer Center
Seattle, Washington, 98106, United States
Northwest Medical Specialties, PLLC
Tacoma, Washington, 98405, United States
Northwest Cancer Specialists - Vancouver
Vancouver, Washington, 98684, United States
Chris OBrien Lifehouse
Camperdown, New South Wales, 2050, Australia
GenesisCare -North Shore Oncology
St Leonards, New South Wales, 2065, Australia
The Queen Elizabeth Hospital
Woodville South, South Australia, 5011, Australia
Austin Health, Austin Hospital
Heidelberg, Victoria, 3084, Australia
Peter MacCallum Cancer Centre
Melbourne, Victoria, 3000, Australia
Epworth Healthcare
St Albans, Victoria, 3021, Australia
Universite Catholique de Louvain Cliniques Universitaires Saint Luc
Brussels, 1200, Belgium
Universitair Ziekenhuis Antwerpen
Edegem, 2650, Belgium
Universitair Ziekenhuis Leuven - Campus Gasthuisberg
Leuven, 3000, Belgium
Arthur J E Child Comprehensive Cancer Centre
Calgary, Alberta, T2N 5G2, Canada
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 1Z5, Canada
CHU de Quebec Hopital de l Enfant Jesus
Québec, Quebec, G1J 1Z4, Canada
Mengchao Hepatobiliary Hospital of Fujian Medical University
Fuzhou, Fujian, 350028, China
Sun Yat-Sen University Cancer Center
Guangzhou, Guangdong, 510030, China
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150000, China
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 450052, China
Union Hospital Tongji Medical College Huazhong University of Science and Technology
Wuhan, Hubei, 430022, China
The First Bethune Hospital of Jilin University
Changchun, Jilin, 130021, China
Herlev og Gentofte Hospital
Herlev, 2730, Denmark
Institut Bergonie
Bordeaux, 33000, France
Centre Georges Francois Leclerc
Dijon, 21000, France
Institut Paoli Calmettes
Marseille, 13009, France
Gustave Roussy
Villejuif, 94805, France
Universitaetsklinikum Essen
Essen, 45147, Germany
Universitaetsklinikum Heidelberg
Heidelberg, 69120, Germany
Universitaetsklinikum Wuerzburg
Würzburg, 97078, Germany
Alexandra Hospital
Athens, 11528, Greece
General Hospital Of Thessaloniki Papageorgiou
Thessaloniki, 56429, Greece
European Interbalkan Medical Center
Thessaloniki, 57001, Greece
Queen Mary Hospital, The University of Hong Kong
Hong Kong, Hong Kong
Prince of Wales Hospital, Chinese University of Hong Kong
Shatin, New Territories, Hong Kong
Fondazione IRCCS Istituto Nazionale dei Tumori
Milan, 20133, Italy
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
Milan, 20162, Italy
IRCCS Istituto Clinico Humanitas
Rozzano MI, 20089, Italy
Centro Ricerche Cliniche Di Verona Societa responsabilita limitata
Verona, 37134, Italy
Aichi Cancer Center
Nagoya, Aichi-ken, 464-8681, Japan
National Cancer Center Hospital East
Kashiwa-shi, Chiba, 277-8577, Japan
Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center
Yokohama, Kanagawa, 241-8515, Japan
National Cancer Center Hospital
Chuo-ku, Tokyo, 104-0045, Japan
Radboud Universitair Medisch Centrum
Nijmegen, 6525 GA, Netherlands
Hospital Universitario Virgen del Rocio
Seville, Andalusia, 41013, Spain
Hospital Universitari Vall d Hebron
Barcelona, Catalonia, 08035, Spain
Hospital General Universitario Gregorio Maranon
Madrid, 28009, Spain
National Cheng Kung University Hospital
Tainan, 70403, Taiwan
National Taiwan University Hospital
Taipei, 10002, Taiwan
Taipei Veterans General Hospital
Taipei, 11217, Taiwan
Queen Elizabeth Hospital Birmingham
Birmingham, B15 2TH, United Kingdom
Sarah Cannon Research Institute UK
London, W1G 6AD, United Kingdom
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY DIRECTOR
MD
Amgen
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
April 8, 2024
First Posted
April 11, 2024
Study Start
May 29, 2024
Primary Completion (Estimated)
February 26, 2027
Study Completion (Estimated)
February 25, 2029
Last Updated
March 31, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
- Access Criteria
- Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.