Advanced Gastrointestinal, Biliary Tract, and Pancreatic Cancers
Conditions
Keywords
Advanced Cancer, Methylthioadenosine Phosphorylase, AMG 193, Oncology
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.
Interventions
DRUGAnvumetostat
Administered Orally
DRUGGemcitabine
Administered IV
DRUGNab-paclitaxel
Administered IV
Modified FOLFIRINOX consists of irinotecan, 5-FU, LV, and oxaliplatin administered IV
DRUGRMC-6236
Administered orally
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
Secondary
| 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 |
| 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) |
| 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) |
Countries
Australia, Belgium, Canada, China, Denmark, France, Germany, Greece, Hong Kong, Italy, Japan, Netherlands, Spain, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORMD
Amgen
CONTACTAmgen Call Center
Outcome results
None listed