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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Gastrointestinal, Biliary Tract, and Pancreatic Cancers
• Intervention / Treatment: Drug: Gemcitabine; Drug: Nab-paclitaxel; Drug: Modified FOLFIRINOX; Drug: RMC-6236; Drug: Anvumetostat

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Chris OBrien Lifehouse
    • St Leonards, New South Wales, Australia, 2065
      • Recruiting
      • GenesisCare -North Shore Oncology
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • Recruiting
      • The Queen Elizabeth Hospital
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Recruiting
      • Austin Health, Austin Hospital
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Centre
    • St Albans, Victoria, Australia, 3021
      • Recruiting
      • Epworth Healthcare
• Belgium
  • Brussels, Belgium, 1200
    • Recruiting
    • Universite Catholique de Louvain Cliniques Universitaires Saint Luc
  • Edegem, Belgium, 2650
    • Recruiting
    • Universitair Ziekenhuis Antwerpen
  • Leuven, Belgium, 3000
    • Recruiting
    • Universitair Ziekenhuis Leuven - Campus Gasthuisberg
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 5G2
      • Recruiting
      • Arthur J E Child Comprehensive Cancer Centre
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z5
      • Recruiting
      • Princess Margaret Cancer Centre
  • Quebec
    • Québec, Quebec, Canada, G1J 1Z4
      • Recruiting
      • CHU de Quebec Hopital de l Enfant Jesus
• China
  • Fujian
    • Fuzhou, Fujian, China, 350028
      • Recruiting
      • Mengchao Hepatobiliary Hospital OF Fujian Medical University
  • Guangdong
    • Guangzhou, Guangdong, China, 510030
      • Recruiting
      • Sun Yat-sen University Cancer Center
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Recruiting
      • Harbin Medical University Cancer Hospital
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Recruiting
      • The First Affiliated Hospital of Zhengzhou University
  • Hubei
    • Wuhan, Hubei, China, 430022
      • Recruiting
      • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Jilin
    • Changchun, Jilin, China, 130021
      • Recruiting
      • The First Bethune Hospital of Jilin University
• Denmark
  • Herlev, Denmark, 2730
    • Recruiting
    • Herlev og Gentofte Hospital
• France
  • Bordeaux, France, 33000
    • Recruiting
    • Institut Bergonié
  • Dijon, France, 21000
    • Recruiting
    • Centre Georges François Leclerc
  • Marseille, France, 13009
    • Recruiting
    • Institut Paoli Calmettes
  • Villejuif, France, 94805
    • Recruiting
    • Gustave Roussy
• Germany
  • Essen, Germany, 45147
    • Recruiting
    • Universitaetsklinikum Essen
  • Heidelberg, Germany, 69120
    • Recruiting
    • Universitaetsklinikum Heidelberg
  • Würzburg, Germany, 97078
    • Recruiting
    • Universitaetsklinikum Wuerzburg
• Greece
  • Athens, Greece, 11528
    • Recruiting
    • Alexandra Hospital
  • Thessaloniki, Greece, 57001
    • Recruiting
    • European Interbalkan Medical Center
  • Thessaloniki, Greece, 56429
    • Recruiting
    • General Hospital Of Thessaloniki Papageorgiou
• Hong Kong
  • Hong Kong, Hong Kong
    • Recruiting
    • Queen Mary Hospital, The University of Hong Kong
  • Shatin, New Territories, Hong Kong
    • Recruiting
    • Prince of Wales Hospital, Chinese University of Hong Kong
• Italy
  • Milan, Italy, 20133
    • Recruiting
    • Fondazione Irccs Istituto Nazionale Dei Tumori
  • Milan, Italy, 20162
    • Recruiting
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
  • Rozzano MI, Italy, 20089
    • Recruiting
    • IRCCS Istituto Clinico Humanitas
  • Verona, Italy, 37134
    • Recruiting
    • Centro Ricerche Cliniche Di Verona Societa responsabilita limitata
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464-8681
      • Recruiting
      • Aichi Cancer Center
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East
  • Kanagawa
    • Yokohama, Kanagawa, Japan, 241-8515
      • Recruiting
      • Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Recruiting
      • National Cancer Center Hospital
• Netherlands
  • Nijmegen, Netherlands, 6525 GA
    • Recruiting
    • Radboud Universitair Medisch Centrum
• Spain
  • Madrid, Spain, 28009
    • Recruiting
    • Hospital General Universitario Gregorio Marañon
  • Andalusia
    • Seville, Andalusia, Spain, 41013
      • Recruiting
      • Hospital Universitario Virgen del Rocio
  • Catalonia
    • Barcelona, Catalonia, Spain, 08035
      • Recruiting
      • Hospital Universitari Vall d Hebron
• Taiwan
  • Tainan, Taiwan, 70403
    • Recruiting
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • Recruiting
    • National Taiwan University Hospital
  • Taipei, Taiwan, 11217
    • Recruiting
    • Taipei Veterans General Hospital
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Recruiting
    • Queen Elizabeth Hospital Birmingham
  • London, United Kingdom, W1G 6AD
    • Recruiting
    • Sarah Cannon Research Institute UK
• United States
  • California
    • Bakersfield, California, United States, 93309
      • Recruiting
      • Comprehensive Blood and Cancer Center
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope National Medical Center
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Orange County Lennar Foundation Cancer Center
    • La Jolla, California, United States, 92093
      • Recruiting
      • University of California San Diego Moores Cancer Center
    • Los Angeles, California, United States, 90095
      • Recruiting
      • Translational Research in Oncology US Inc, Trio Central Pharmacy
    • Santa Monica, California, United States, 90404
      • Recruiting
      • University of California Los Angeles
  • Colorado
    • Aurora, Colorado, United States, 80012
      • Recruiting
      • Rocky Mountain Cancer Centers
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Recruiting
      • Hartford Hospital
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale University
    • Norwalk, Connecticut, United States, 06856
      • Recruiting
      • Norwalk Hospital
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Recruiting
      • Indiana University
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Norton Cancer Institute
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • Recruiting
      • University of Nebraska
  • Nevada
    • Las Vegas, Nevada, United States, 89169
      • Terminated
      • Comprehensive Cancer Centers of Nevada
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic Foundation
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • United States Oncology Regulatory Affairs Corporate Office
  • Texas
    • Houston, Texas, United States, 77030
      • Terminated
      • Oncology Consultants Cancer Center
    • Irving, Texas, United States, 75063
      • Recruiting
      • US Oncology Research Investigational Products Center
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Recruiting
      • University of Virginia Cancer Center
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists PC
  • Washington
    • Seattle, Washington, United States, 98106
      • Recruiting
      • Fred Hutchinson Cancer Center
    • Tacoma, Washington, United States, 98405
      • Recruiting
      • Northwest Medical Specialties, PLLC
    • Vancouver, Washington, United States, 98684
      • Completed
      • Northwest Cancer Specialists - Vancouver

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Subprotocol B

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.
• 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 Anvumetostat.
• Cardiovascular and pulmonary exclusion criteria as defined in the protocol.
• 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.
• Cardiovascular and pulmonary exclusion criteria as defined in the protocol.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Subprotocol B: Pancreatic Ductal Adenocarcinoma (PDAC) Arm A; Part 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.	Drug: Gemcitabine; Administered IV; Drug: Nab-paclitaxel; Administered IV; Drug: Anvumetostat; Administered Orally; Other Names: AMG 193
Experimental: Subprotocol B: PDAC Arm B; Part 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.	Drug: Modified FOLFIRINOX; Modified FOLFIRINOX consists of irinotecan, 5-FU, LV, and oxaliplatin administered IV; Drug: Anvumetostat; Administered Orally; Other Names: AMG 193
Experimental: Subprotocol C: Dose Exploration; Part 1: Participants with MTAP-deleted PDAC will receive oral doses of Anvumetostat and RMC-6236.	Drug: RMC-6236; Administered orally; Drug: Anvumetostat; Administered Orally; Other Names: AMG 193
Experimental: Subprotocol C: Dose Expansion; Part 2: Participants with MTAP-deleted PDAC will receive oral doses of Anvumetostat andRMC-6236.	Drug: RMC-6236; Administered orally; Drug: Anvumetostat; Administered Orally; Other Names: AMG 193

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Time Frame
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
Progression-free Survival (PFS) per RECIST v1.1	Up to approximately 2 years
Cmax of RMC-6236	Up to Day 1 of Cycle 5 (one cycle = 21 days)
Tmax of RMC-6236	Up to Day 1 of Cycle 5 (one cycle = 21 days)
AUC of RMC-6236	Up to Day 1 of Cycle 5 (one cycle = 21 days)
Maximum Plasma Concentration (Cmax) of Anvumetostat	Up to Day 1 of Cycle 5 (one cycle = 21 or 28 days)
Time to Maximum Plasma Concentration (tmax) of Anvumetostat	Up to Day 1 of Cycle 5 (one cycle = 21 or 28 days)
Area Under the Plasma Concentration-time Curve (AUC) of Anvumetostat	Up to Day 1 of Cycle 5 (one cycle = 21 or 28 days)

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2024
• Primary Completion (Estimated): February 26, 2027
• Study Completion (Estimated): February 25, 2029

Study Registration Dates

• First Submitted: April 8, 2024
• First Submitted That Met QC Criteria: April 8, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Actual): March 31, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Oncology; Advanced Cancer; AMG 193; Methylthioadenosine Phosphorylase
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Neoplasms; Pancreatic Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Gemcitabine; 130-nm albumin-bound paclitaxel
• Other Study ID Numbers: 20230223

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No