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 - Master Protocol AMG 193 in Combination with mFOLFIRINOX or with Gemcitabine and Nab-paclitaxel in Subjects with Advanced PDAC with Homozygous MTAP-deletion (Subprotocol B)

JRCT ID: jRCT2031240376

Registered date:07/10/2024

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Pancreatic Cancers
• Date of first enrollment: 29/05/2024
• Target sample size: 188
• Countries of recruitment: United States,Japan
• Study type: Interventional

Intervention(s)

- Experimental: Subprotocol B: Pancreatic Ductal Adenocarcinoma (PDAC) Arm A
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.
Interventions:
- Drug: AMG 193
- Drug: Gemcitabine
- Drug: Nab-paclitaxel

- Experimental: Subprotocol B: PDAC Arm B
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.
Interventions:
- Drug: AMG 193
- Drug: Modified FOLFIRINOX

Outcome(s)

Primary Outcome

1. Number of Participants Experiencing Dose Limiting Toxicities (DLT) [Time Frame: Up to 28 days]
2. Number of Participants Experiencing Treatment Emergent Adverse Events (TEAE) [Time Frame: Up to approximately 2 years]
Any clinically significant changes in vital signs, electrocardiogram, or lab parameters will be recorded as TEAEs.
3. Number of Participants Experiencing Serious Adverse Events (SAE) [Time Frame: Up to approximately 2 years]

Secondary Outcome

1. Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1) [Time Frame: Up to approximately 2 years]
2. Disease Control (DC) per RECIST v1.1 [Time Frame: Up to approximately 2 years]
3. Duration of Response (DOR) per RECIST v1.1 [Time Frame: Up to approximately 2 years]
4. Time to Response (TTR) per RECIST v1.1 [Time Frame: Up to approximately 2 years]
5. Overall Survival (OS) per RECIST v1.1 [Time Frame: Up to approximately 2 years]
6. Progression-free Survival (PFS) per RECIST v1.1 [Time Frame: Up to approximately 2 years]
7. Maximum Plasma Concentration (Cmax) of AMG193 [Time Frame: Up to Day 1 of Cycle 5 (one cycle = 21 or 28 days)]
8. Time to Maximum Plasma Concentration (tmax) of AMG193 [Time Frame: Up to Day 1 of Cycle 5 (one cycle = 21 or 28 days)]
9. Area Under the Plasma Concentration-time Curve (AUC) of AMG 193 [Time Frame: Up to Day 1 of Cycle 5 (one cycle = 21 or 28 days)]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

Subprotocol B
1. Age >= 18 years (or >= legal age within the country if it is older than 18 years).
2. Histologically or cytologically confirmed diagnosis of metastatic and/or unresectable (locally advanced) adenocarcinoma of the pancreas.
3. 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.
4. Homozygous MTAP-deletion.
5. Disease measurable as defined by RECIST v1.1.
6. Adequate organ function as defined in the protocol

Exclude criteria

Subprotocol B
1. Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor.
2. Radiation therapy within 28 days of first dose.
3. Major surgery within 28 days of first dose of AMG 193.
4. Cardiovascular and pulmonary exclusion criteria as defined in the protocol.
5. 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).
6. History of solid organ transplantation.

Related Information

• Primary Sponsor: Iizumi Sakura
• Secondary ID(s): NCT06360354