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)
Purpose
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.
Condition
- Advanced Gastrointestinal, Biliary Tract, and Pancreatic Cancers
Eligibility
- Eligible Ages
- Between 18 Years and 100 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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 AMG 193.
- 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
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- Non-Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Subprotocol B: Pancreatic Ductal Adenocarcinoma (PDAC) Arm A |
Part 1: Participants with MTAP-deleted PDAC will receive doses of AMG 193 orally in combination with gemcitabine and nab-paclitaxel IV. Part 2: Participants with MTAP-deleted PDAC will receive the recommended dose of AMG 193 in combination with gemcitabine and nab-paclitaxel. |
|
|
Experimental Subprotocol B: PDAC Arm B |
Part 1: Participants with MTAP-deleted PDAC will receive doses of AMG 193 orally in combination with mFOLFIRINOX (irinotecan, fluorouracil, leucovorin calcium, oxaliplatin) IV. Part 2: Participants with MTAP-deleted PDAC will receive the recommended dose of AMG 193 in combination with mFOLFIRINOX. |
|
|
Experimental Subprotocol C: Dose Exploration |
Part 1: Participants with MTAP-deleted PDAC will receive oral doses of AMG 193 and RMC-6236. |
|
|
Experimental Subprotocol C: Dose Expansion |
Part 2: Participants with MTAP-deleted PDAC will receive oral doses of AMG 193 andRMC-6236. |
|
Recruiting Locations
Bakersfield 5325738, California 5332921 93309
Duarte 5344147, California 5332921 91010
Duarte 5344147, California 5332921 91010
La Jolla 5363943, California 5332921 92093
Los Angeles 5368361, California 5332921 90095
Santa Monica 5393212, California 5332921 90404
Aurora 5412347, Colorado 5417618 80012
Hartford 4835797, Connecticut 4831725 06106
New Haven 4839366, Connecticut 4831725 06520
Norwalk 4839822, Connecticut 4831725 06856
Chicago 4887398, Illinois 4896861 60637
Indianapolis 4259418, Indiana 4921868 46202
Louisville 4299276, Kentucky 6254925 40202
Boston 4930956, Massachusetts 6254926 02215
Boston 4930956, Massachusetts 6254926 02215
St Louis 4407066, Missouri 4398678 63110
Omaha 5074472, Nebraska 5073708 68198
New York 5128581, New York 5128638 10065
Durham 4464368, North Carolina 4482348 27710
Cleveland 5150529, Ohio 5165418 44195
Nashville 4644585, Tennessee 4662168 37203
Irving 4700168, Texas 4736286 75063
Charlottesville 4752031, Virginia 6254928 22903
Fairfax 4758023, Virginia 6254928 22031
Seattle 5809844, Washington 5815135 98106
Tacoma 5812944, Washington 5815135 98405
Vancouver 5814616, Washington 5815135 98684
More Details
- NCT ID
- NCT06360354
- Status
- Recruiting
- Sponsor
- Amgen