A Study Evaluating AMG 193 in Combination With Other Therapies in Participants With Advanced Gastrointestinal, Biliary Tract, or Pancreatic Cancers With Homozygous Methylthioadenosine Phosphorylase (MTAP)-Deletion (MTAPESTRY 103)
A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 193 in Combination With Other Therapies in Subjects With Advanced Gastrointestinal, Biliary Tract, or Pancreatic Cancers With Homozygous MTAP-deletion
Amgen
350 participants
May 29, 2024
INTERVENTIONAL
Conditions
Summary
The study aims to determine maximum tolerated dose (MTD) or recommended combination dose of the MTA-cooperative PRMT5 inhibitor AMG 193 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 AMG 193 administered in combination with other therapies in adult participants with metastatic or locally advanced MTAP-deleted gastrointestinal, biliary tract, or pancreatic cancers.
Eligibility
Inclusion Criteria14
- Subprotocol B
- 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.
- 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 Criteria9
- 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 AMG 193.
- 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
- 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).
- History of solid organ transplantation.
Interventions
Administered Orally
Administered IV
Administered IV
Modified FOLFIRINOX consists of irinotecan, 5-FU, LV, and oxaliplatin administered IV
Administered orally
Locations(77)
View Full Details on ClinicalTrials.gov
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NCT06360354