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)

NCT06360354 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: 20230223
• Study Type: interventional
• Target: 120
• Locations: 16 countries
• Sites: 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.

Conditions

Advanced Gastrointestinal, Biliary Tract, and Pancreatic Cancers

Keywords

Advanced Cancer; Methylthioadenosine Phosphorylase; AMG 193; Oncology

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

Study Arms (4)

Subprotocol B: Pancreatic Ductal Adenocarcinoma (PDAC) Arm A

EXPERIMENTAL

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: Anvumetostat; Drug: Gemcitabine; Drug: Nab-paclitaxel

Subprotocol B: PDAC Arm B

EXPERIMENTAL

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: Anvumetostat; Drug: Modified FOLFIRINOX

Subprotocol C: Dose Exploration

EXPERIMENTAL

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

Drug: Anvumetostat; Drug: RMC-6236

Subprotocol C: Dose Expansion

EXPERIMENTAL

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

Drug: Anvumetostat; Drug: RMC-6236

Interventions

Gemcitabine DRUG

Administered IV

Subprotocol B: Pancreatic Ductal Adenocarcinoma (PDAC) Arm A

Nab-paclitaxel DRUG

Administered IV

Subprotocol B: Pancreatic Ductal Adenocarcinoma (PDAC) Arm A

Modified FOLFIRINOX DRUG

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

Subprotocol B: PDAC Arm B

RMC-6236 DRUG

Administered orally

Subprotocol C: Dose Expansion; Subprotocol C: Dose Exploration

Anvumetostat DRUG

Administered Orally

Also known as: AMG 193

Subprotocol B: PDAC Arm B; Subprotocol B: Pancreatic Ductal Adenocarcinoma (PDAC) Arm A; Subprotocol C: Dose Expansion; Subprotocol C: Dose Exploration

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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).

Sponsors & Collaborators

• Amgen: lead

Study Sites (77)

Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

Location

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

City of Hope Orange County Lennar Foundation Cancer Center

Duarte, California, 91010, United States

Location

University of California San Diego Moores Cancer Center

La Jolla, California, 92093, United States

Location

Translational Research in Oncology US Inc, Trio Central Pharmacy

Los Angeles, California, 90095, United States

Location

University of California Los Angeles

Santa Monica, California, 90404, United States

Location

Rocky Mountain Cancer Centers

Aurora, Colorado, 80012, United States

Location

Hartford Hospital

Hartford, Connecticut, 06106, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Norwalk Hospital

Norwalk, Connecticut, 06856, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

University of Nebraska

Omaha, Nebraska, 68198, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

United States Oncology Regulatory Affairs Corporate Office

Nashville, Tennessee, 37203, United States

Location

Oncology Consultants Cancer Center

Houston, Texas, 77030, United States

Location

US Oncology Research Investigational Products Center

Irving, Texas, 75063, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22903, United States

Location

Virginia Cancer Specialists PC

Fairfax, Virginia, 22031, United States

Location

Fred Hutchinson Cancer Center

Seattle, Washington, 98106, United States

Location

Northwest Medical Specialties, PLLC

Tacoma, Washington, 98405, United States

Location

Northwest Cancer Specialists - Vancouver

Vancouver, Washington, 98684, United States

Location

Chris OBrien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

GenesisCare -North Shore Oncology

St Leonards, New South Wales, 2065, Australia

Location

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

Location

Austin Health, Austin Hospital

Heidelberg, Victoria, 3084, Australia

Location

Peter MacCallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Epworth Healthcare

St Albans, Victoria, 3021, Australia

Location

Universite Catholique de Louvain Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Arthur J E Child Comprehensive Cancer Centre

Calgary, Alberta, T2N 5G2, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1Z5, Canada

Location

CHU de Quebec Hopital de l Enfant Jesus

Québec, Quebec, G1J 1Z4, Canada

Location

Mengchao Hepatobiliary Hospital of Fujian Medical University

Fuzhou, Fujian, 350028, China

Location

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510030, China

Location

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150000, China

Location

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

Location

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

The First Bethune Hospital of Jilin University

Changchun, Jilin, 130021, China

Location

Herlev og Gentofte Hospital

Herlev, 2730, Denmark

Location

Institut Bergonie

Bordeaux, 33000, France

Location

Centre Georges Francois Leclerc

Dijon, 21000, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Universitaetsklinikum Essen

Essen, 45147, Germany

Location

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitaetsklinikum Wuerzburg

Würzburg, 97078, Germany

Location

Alexandra Hospital

Athens, 11528, Greece

Location

General Hospital Of Thessaloniki Papageorgiou

Thessaloniki, 56429, Greece

Location

European Interbalkan Medical Center

Thessaloniki, 57001, Greece

Location

Queen Mary Hospital, The University of Hong Kong

Hong Kong, Hong Kong

Location

Prince of Wales Hospital, Chinese University of Hong Kong

Shatin, New Territories, Hong Kong

Location

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

Location

IRCCS Istituto Clinico Humanitas

Rozzano MI, 20089, Italy

Location

Centro Ricerche Cliniche Di Verona Societa responsabilita limitata

Verona, 37134, Italy

Location

Aichi Cancer Center

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

Location

Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center

Yokohama, Kanagawa, 241-8515, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Radboud Universitair Medisch Centrum

Nijmegen, 6525 GA, Netherlands

Location

Hospital Universitario Virgen del Rocio

Seville, Andalusia, 41013, Spain

Location

Hospital Universitari Vall d Hebron

Barcelona, Catalonia, 08035, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28009, Spain

Location

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Queen Elizabeth Hospital Birmingham

Birmingham, B15 2TH, United Kingdom

Location

Sarah Cannon Research Institute UK

London, W1G 6AD, United Kingdom

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Pancreatic Neoplasms; Neoplasms

Interventions

Gemcitabine; 130-nm albumin-bound paclitaxel

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

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): October 31, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: June 1, 2026

Record last verified: 2026-05

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.

Locations

DE (3); CN (6); CA (3); GB (2); JP (4); HK (2); TW (3); BE (3); GR (3); AU (6); DK (1); US (29); FR (4); IT (4); ES (3); NL (1)