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

Amgen

Status and phase: Enrolling; Phase 1

Conditions: Advanced Gastrointestinal, Biliary Tract, and Pancreatic Cancers

Treatments: Drug: Gemcitabine; Drug: AMG 193; Drug: Nab-paclitaxel; Drug: Modified FOLFIRINOX

Study type: Interventional

Funder types: Industry

Identifiers

NCT06360354

20230223

Details and patient eligibility

About

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.

Enrollment: 188 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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188 participants in 2 patient groups

Subprotocol B: Pancreatic Ductal Adenocarcinoma (PDAC) Arm A

Experimental group

Description:

Part 1: Participants with MTAP-deleted PDAC will receive escalating 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.

Treatment:

Drug: Nab-paclitaxel

Drug: Gemcitabine

Drug: AMG 193

Subprotocol B: PDAC Arm B

Experimental group

Description:

Part 1: Participants with MTAP-deleted PDAC will receive escalating 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.

Treatment:

Drug: Modified FOLFIRINOX

Drug: AMG 193