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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 · Amgen
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Official title
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
About this study
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.
Eligibility criteria
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 design
Enrollment target: 350 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-05-29
Estimated completion: 2029-02-25
Last updated: 2026-03-31
Interventions
Drug: AnvumetostatDrug: GemcitabineDrug: Nab-paclitaxelDrug: Modified FOLFIRINOXDrug: RMC-6236
Primary outcomes
  • Number of Participants Experiencing Dose Limiting Toxicities (DLT) (Up to 28 days)
  • Number of Participants Experiencing Treatment Emergent Adverse Events (TEAE) (Up to approximately 2 years)
  • Number of Participants Experiencing Serious Adverse Events (SAE) (Up to approximately 2 years)
Sponsor
Amgen · industry
Contacts & investigators
ContactAmgen Call Center · contact · medinfo@amgen.com · 866-572-6436
InvestigatorMD · study_director, Amgen
All locations (77)
Comprehensive Blood and Cancer CenterRecruiting
Bakersfield, California, United States
City of Hope National Medical CenterRecruiting
Duarte, California, United States
City of Hope Orange County Lennar Foundation Cancer CenterRecruiting
Duarte, California, United States
University of California San Diego Moores Cancer CenterRecruiting
La Jolla, California, United States
Translational Research in Oncology US Inc, Trio Central PharmacyRecruiting
Los Angeles, California, United States
University of California Los AngelesRecruiting
Santa Monica, California, United States
Rocky Mountain Cancer CentersRecruiting
Aurora, Colorado, United States
Hartford HospitalRecruiting
Hartford, Connecticut, United States
Yale UniversityRecruiting
New Haven, Connecticut, United States
Norwalk HospitalRecruiting
Norwalk, Connecticut, United States
University of ChicagoRecruiting
Chicago, Illinois, United States
Indiana UniversityRecruiting
Indianapolis, Indiana, United States
Norton Cancer InstituteRecruiting
Louisville, Kentucky, United States
Beth Israel Deaconess Medical CenterRecruiting
Boston, Massachusetts, United States
Dana-Farber Cancer InstituteRecruiting
Boston, Massachusetts, United States
Washington UniversityRecruiting
St Louis, Missouri, United States
University of NebraskaRecruiting
Omaha, Nebraska, United States
Comprehensive Cancer Centers of NevadaTerminated
Las Vegas, Nevada, United States
Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
Duke UniversityRecruiting
Durham, North Carolina, United States
Cleveland Clinic FoundationRecruiting
Cleveland, Ohio, United States
United States Oncology Regulatory Affairs Corporate OfficeRecruiting
Nashville, Tennessee, United States
Oncology Consultants Cancer CenterTerminated
Houston, Texas, United States
US Oncology Research Investigational Products CenterRecruiting
Irving, Texas, United States
University of Virginia Cancer CenterRecruiting
Charlottesville, Virginia, United States
Virginia Cancer Specialists PCRecruiting
Fairfax, Virginia, United States
Fred Hutchinson Cancer CenterRecruiting
Seattle, Washington, United States
Northwest Medical Specialties, PLLCRecruiting
Tacoma, Washington, United States
Northwest Cancer Specialists - VancouverCompleted
Vancouver, Washington, United States
Chris OBrien LifehouseRecruiting
Camperdown, New South Wales, Australia
GenesisCare -North Shore OncologyRecruiting
St Leonards, New South Wales, Australia
The Queen Elizabeth HospitalRecruiting
Woodville South, South Australia, Australia
Austin Health, Austin HospitalRecruiting
Heidelberg, Victoria, Australia
Peter MacCallum Cancer CentreRecruiting
Melbourne, Victoria, Australia
Epworth HealthcareRecruiting
St Albans, Victoria, Australia
Universite Catholique de Louvain Cliniques Universitaires Saint LucRecruiting
Brussels, Belgium
Universitair Ziekenhuis AntwerpenRecruiting
Edegem, Belgium
Universitair Ziekenhuis Leuven - Campus GasthuisbergRecruiting
Leuven, Belgium
Arthur J E Child Comprehensive Cancer CentreRecruiting
Calgary, Alberta, Canada
Princess Margaret Cancer CentreRecruiting
Toronto, Ontario, Canada
CHU de Quebec Hopital de l Enfant JesusRecruiting
Québec, Quebec, Canada
Mengchao Hepatobiliary Hospital of Fujian Medical UniversityRecruiting
Fuzhou, Fujian, China
Sun Yat-Sen University Cancer CenterRecruiting
Guangzhou, Guangdong, China
Harbin Medical University Cancer HospitalRecruiting
Harbin, Heilongjiang, China
The First Affiliated Hospital of Zhengzhou UniversityRecruiting
Zhengzhou, Henan, China
Union Hospital Tongji Medical College Huazhong University of Science and TechnologyRecruiting
Wuhan, Hubei, China
The First Bethune Hospital of Jilin UniversityRecruiting
Changchun, Jilin, China
Herlev og Gentofte HospitalRecruiting
Herlev, Denmark
Institut BergonieRecruiting
Bordeaux, France
Centre Georges Francois LeclercRecruiting
Dijon, France
Institut Paoli CalmettesRecruiting
Marseille, France
Gustave RoussyRecruiting
Villejuif, France
Universitaetsklinikum EssenRecruiting
Essen, Germany
Universitaetsklinikum HeidelbergRecruiting
Heidelberg, Germany
Universitaetsklinikum WuerzburgRecruiting
Würzburg, Germany
Alexandra HospitalRecruiting
Athens, Greece
General Hospital Of Thessaloniki PapageorgiouRecruiting
Thessaloniki, Greece
European Interbalkan Medical CenterRecruiting
Thessaloniki, Greece
Queen Mary Hospital, The University of Hong KongRecruiting
Hong Kong, Hong Kong
Prince of Wales Hospital, Chinese University of Hong KongRecruiting
Shatin, New Territories, Hong Kong
Fondazione IRCCS Istituto Nazionale dei TumoriRecruiting
Milan, Italy
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano NiguardaRecruiting
Milan, Italy
IRCCS Istituto Clinico HumanitasRecruiting
Rozzano MI, Italy
Centro Ricerche Cliniche Di Verona Societa responsabilita limitataRecruiting
Verona, Italy
Aichi Cancer CenterRecruiting
Nagoya, Aichi-ken, Japan
National Cancer Center Hospital EastRecruiting
Kashiwa-shi, Chiba, Japan
Kanagawa Prefectural Hospital Organization Kanagawa Cancer CenterRecruiting
Yokohama, Kanagawa, Japan
National Cancer Center HospitalRecruiting
Chuo-ku, Tokyo, Japan
Radboud Universitair Medisch CentrumRecruiting
Nijmegen, Netherlands
Hospital Universitario Virgen del RocioRecruiting
Seville, Andalusia, Spain
Hospital Universitari Vall d HebronRecruiting
Barcelona, Catalonia, Spain
Hospital General Universitario Gregorio MaranonRecruiting
Madrid, Spain
National Cheng Kung University HospitalRecruiting
Tainan, Taiwan
National Taiwan University HospitalRecruiting
Taipei, Taiwan
Taipei Veterans General HospitalRecruiting
Taipei, Taiwan
Queen Elizabeth Hospital BirminghamRecruiting
Birmingham, United Kingdom
Sarah Cannon Research Institute UKRecruiting
London, United Kingdom
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) · TrialPath