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

Phase 1

Recruiting

• Conditions: Advanced Gastrointestinal, Biliary Tract, and Pancreatic Cancers
• Interventions: Drug: AMG 193; Drug: Modified FOLFIRINOX; Drug: Gemcitabine; Drug: Nab-paclitaxel

• Registration Number: NCT06360354
• Lead Sponsor: Amgen

Brief 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-04-08
• Study First Submitted QC: 2024-04-08
• Study First Posted: 2024-04-11
• Study Start: 2024-05-29
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-23
• Last Update Posted: 2025-04-24
• Primary Completion: 2027-02-26
• Study Completion: 2029-02-25

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 188

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Subprotocol B: Pancreatic Ductal Adenocarcinoma (PDAC) Arm A	AMG 193	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.
Subprotocol B: Pancreatic Ductal Adenocarcinoma (PDAC) Arm A	Nab-paclitaxel	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.
Subprotocol B: PDAC Arm B	Modified FOLFIRINOX	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.
Subprotocol B: PDAC Arm B	AMG 193	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.
Subprotocol B: Pancreatic Ductal Adenocarcinoma (PDAC) Arm A	Gemcitabine	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.

Primary Outcome Measures

Name	Time	Method
Number of Participants Experiencing Dose Limiting Toxicities (DLT)	Up to 28 days
Number of Participants Experiencing Serious Adverse Events (SAE)	Up to approximately 2 years
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.

Secondary Outcome Measures

Name	Time	Method
Time to Response (TTR) per RECIST v1.1	Up to approximately 2 years
Time to Maximum Plasma Concentration (tmax) of AMG193	Up to Day 1 of Cycle 5 (one cycle = 21 or 28 days)
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
Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (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 AMG193	Up to Day 1 of Cycle 5 (one cycle = 21 or 28 days)
Area Under the Plasma Concentration-time Curve (AUC) of AMG 193	Up to Day 1 of Cycle 5 (one cycle = 21 or 28 days)

Trial Locations

Locations (71)

Beth Israel Deaconess Medical Center; 🇺🇸 Boston, Massachusetts, United States

Comprehensive Blood and Cancer Center; 🇺🇸 Bakersfield, California, United States

City of Hope National Medical Center; 🇺🇸 Duarte, California, United States

University of California San Diego Moores Cancer Center; 🇺🇸 La Jolla, California, United States

Translational Research in Oncology US Inc, Trio Central Pharmacy; 🇺🇸 Los Angeles, California, United States

University of California Los Angeles; 🇺🇸 Santa Monica, California, United States

Rocky Mountain Cancer Centers; 🇺🇸 Aurora, Colorado, United States

Hartford Hospital; 🇺🇸 Hartford, Connecticut, United States

Yale University; 🇺🇸 New Haven, Connecticut, United States

Norwalk Hospital; 🇺🇸 Norwalk, Connecticut, United States

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