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

April 19, 2024 updated by: Amgen

A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 193 in Combination With Other Therapies in Subjects With Advanced Gastrointestinal, Biliary Tract, or Pancreatic Cancers With Homozygous MTAP-deletion

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

282

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Duarte, California, United States, 91010
        • Recruiting
        • City of Hope National Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Subprotocol A

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) biliary tract cancer (intra- or extrahepatic cholangiocarcinoma or gallbladder cancer).
  • Tumor tissue (formalin-fixed, paraffin-embedded [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 AMG 193 dosing.
  • Homozygous MTAP-deletion.
  • Disease measurable as defined by RECIST v1.1.
  • Adequate organ function as defined in the protocol

Exclusion:

  • Major surgery within 28 days of first dose of AMG 193.
  • Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor.
  • Radiation therapy within 28 days of first dose.
  • 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 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Subprotocol A: Biliary Tract Cancer (BTC)

Part 1: Participants with MTAP-deleted BTC will receive escalating doses of AMG 193 orally in combination with gemcitabine, cisplatin, and pembrolizumab intravenously (IV).

Part 2: Participants with MTAP-deleted BTC will receive the recommended dose of AMG 193 in combination with gemcitabine, cisplatin, and pembrolizumab.
Drug: Pembrolizumab
Administered IV
Drug: Cisplatin
Administered IV
Drug: Gemcitabine
Administered IV
Drug: AMG 193
Administered Orally
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.
Drug: Gemcitabine
Administered IV
Drug: Nab-paclitaxel
Administered IV
Drug: AMG 193
Administered Orally
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.
Drug: AMG 193
Administered Orally
Drug: Modified FOLFIRINOX
Modified FOLFIRINOX consists of irinotecan, 5-FU, LV, and oxaliplatin administered IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Experiencing Dose Limiting Toxicities (DLT)
Time Frame: Up to 28 days
Up to 28 days
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.
Up to approximately 2 years
Number of Participants Experiencing Serious Adverse Events (SAE)
Time Frame: Up to approximately 2 years
Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
Time Frame: Up to approximately 2 years
Up to approximately 2 years
Disease Control (DC) per RECIST v1.1
Time Frame: Up to approximately 2 years
Up to approximately 2 years
Duration of Response (DOR) per RECIST v1.1
Time Frame: Up to approximately 2 years
Up to approximately 2 years
Time to Response (TTR) per RECIST v1.1
Time Frame: Up to approximately 2 years
Up to approximately 2 years
Overall Survival (OS) per RECIST v1.1
Time Frame: Up to approximately 2 years
Up to approximately 2 years
Progression-free Survival (PFS) per RECIST v1.1
Time Frame: Up to approximately 2 years
Up to approximately 2 years
Maximum Plasma Concentration (Cmax) of AMG193
Time Frame: Up to Day 1 of Cycle 5 (one cycle = 21 or 28 days)
Up to Day 1 of Cycle 5 (one cycle = 21 or 28 days)
Time to Maximum Plasma Concentration (tmax) of AMG193
Time Frame: Up to Day 1 of Cycle 5 (one cycle = 21 or 28 days)
Up to Day 1 of Cycle 5 (one cycle = 21 or 28 days)
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)
Up to Day 1 of Cycle 5 (one cycle = 21 or 28 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Amgen

Investigators

  • Study Director: MD, Amgen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 1, 2024

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

June 29, 2028

Study Registration Dates

First Submitted

April 8, 2024

First Submitted That Met QC Criteria

April 8, 2024

First Posted (Actual)

April 11, 2024

Study Record Updates

Last Update Posted (Actual)

April 22, 2024

Last Update Submitted That Met QC Criteria

April 19, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20230223

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

IPD Sharing Time Frame

Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.

IPD Sharing Access Criteria

Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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