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Active, not recruiting Phase 1

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 · tracked via the Priya Life Science Netherlands tracker
Sponsor
Phase
Phase 1
Started
2024-05-29
Last updated
2026-06-01

Condition(s) studied

Advanced Gastrointestinal, Biliary Tract, and Pancreatic Cancers

Investigational drug(s) / intervention(s)

Anvumetostat →Gemcitabine →Nab-paclitaxel →Modified FOLFIRINOX →RMC-6236 →

Anvumetostat: Administered Orally

Gemcitabine: Administered IV

Nab-paclitaxel: Administered IV

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

RMC-6236: Administered orally

Study 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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
100 Years
Healthy volunteers
No
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.

Primary outcome measure(s)

  • 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
    Any clinically significant changes in vital signs, electrocardiogram, or lab parameters will be recorded as TEAEs.
  • Number of Participants Experiencing Serious Adverse Events (SAE) — Up to approximately 2 years

Trial sites (77)

FacilityCityRegionStatus
Comprehensive Blood and Cancer Center Bakersfield California
City of Hope National Medical Center Duarte California
City of Hope Orange County Lennar Foundation Cancer Center Duarte California
University of California San Diego Moores Cancer Center La Jolla California
Translational Research in Oncology US Inc, Trio Central Pharmacy Los Angeles California
University of California Los Angeles Santa Monica California
Rocky Mountain Cancer Centers Aurora Colorado
Hartford Hospital Hartford Connecticut
Yale University New Haven Connecticut
Norwalk Hospital Norwalk Connecticut
University of Chicago Chicago Illinois
Indiana University Indianapolis Indiana
Norton Cancer Institute Louisville Kentucky
Beth Israel Deaconess Medical Center Boston Massachusetts
Dana-Farber Cancer Institute Boston Massachusetts
Washington University St Louis Missouri
University of Nebraska Omaha Nebraska
Comprehensive Cancer Centers of Nevada Las Vegas Nevada
Memorial Sloan Kettering Cancer Center New York New York
Duke University Durham North Carolina
Cleveland Clinic Foundation Cleveland Ohio
United States Oncology Regulatory Affairs Corporate Office Nashville Tennessee
Oncology Consultants Cancer Center Houston Texas
US Oncology Research Investigational Products Center Irving Texas
University of Virginia Cancer Center Charlottesville Virginia
Virginia Cancer Specialists PC Fairfax Virginia
Fred Hutchinson Cancer Center Seattle Washington
Northwest Medical Specialties, PLLC Tacoma Washington
Northwest Cancer Specialists - Vancouver Vancouver Washington
Chris OBrien Lifehouse Camperdown New South Wales
GenesisCare -North Shore Oncology St Leonards New South Wales
The Queen Elizabeth Hospital Woodville South South Australia
Austin Health, Austin Hospital Heidelberg Victoria
Peter MacCallum Cancer Centre Melbourne Victoria
Epworth Healthcare St Albans Victoria
Universite Catholique de Louvain Cliniques Universitaires Saint Luc Brussels Belgium
Universitair Ziekenhuis Antwerpen Edegem Belgium
Universitair Ziekenhuis Leuven - Campus Gasthuisberg Leuven Belgium
Arthur J E Child Comprehensive Cancer Centre Calgary Alberta
Princess Margaret Cancer Centre Toronto Ontario

+ 37 more sites — see the full list on the official registry below.

Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT06360354 on ClinicalTrials.gov ↗ ← All trials in the Netherlands