A Study of AMG 193 in Participants With Advanced MTAP-null Solid Tumors (MTAPESTRY 101)

NCT ID: NCT05094336

Last Updated: 2025-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

649 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-02-01

Study Completion Date

2028-06-01

Brief Summary

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The primary objective of Parts 1 and 2 of this study is to evaluate the safety, tolerability, and to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of AMG 193 alone and in combination with docetaxel in adult participants with metastatic or locally advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors.

The primary objective of Part 3 of this study is to evaluate the efficacy of AMG 193 in adult participants with metastatic or locally advanced MTAP-null solid tumors.

Detailed Description

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Conditions

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Advanced MTAP-null Solid Tumors

Keywords

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Metastatic MTAP-null solid tumors Advanced MTAP-null solid tumors Non-small cell lung cancer Biliary Tract Cancer (BTC) Head and neck squamous cell carcinoma Pancreatic adenocarcinoma Esophageal cancer Gastric cancer Glioma

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1a, Phase 1: AMG 193 Monotherapy Dose Exploration

Participants with MTAP-null solid tumors will receive escalating doses of AMG 193 to estimate the MTD and/or the RP2D.

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

AMG 193: Orally via tablet

Part 1c, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified MTD/RP2D of AMG 193 in the following cohort: MTAP-null NSCLC.

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

AMG 193: Orally via tablet

Part 2a, Phase 1: AMG 193 Dose Exploration + Docetaxel

Participants with MTAP-null NSCLC will receive escalating doses of AMG 193 + a fixed dose of docetaxel to estimate the MTD/RP2D of the combination.

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

AMG 193: Orally via tablet

Docetaxel

Intervention Type DRUG

Docetaxel: Intravenous infusion

Part 2b, Phase 1: AMG 193 + Docetaxel Dose Expansion

Participants with MTAP-null NSCLC will receive the identified MTD/RP2D of AMG 193 + docetaxel.

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

AMG 193: Orally via tablet

Docetaxel

Intervention Type DRUG

Docetaxel: Intravenous infusion

Part 3: AMG 193 Phase 2

Participants with MTAP-null solid tumors will receive AMG 193.

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

AMG 193: Orally via tablet

Part 1e, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null BTC.

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

AMG 193: Orally via tablet

Part 1f, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort:

MTAP-null head and neck squamous cell carcinoma (HNSCC).

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

AMG 193: Orally via tablet

Part 1g, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort:

MTAP-null pancreatic adenocarcinoma.

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

AMG 193: Orally via tablet

Part 1h, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null or lost MTAP expression solid tumors (other than lymphoma or primary brain tumor).

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

AMG 193: Orally via tablet

Part 1i, Phase 1: AMG 193 Dose Optimization

Participants will receive a randomized dose optimization evaluation of AMG 193.

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

AMG 193: Orally via tablet

Part 1j, Phase 1: AMG 193 DSPS Substudy (US Sites Only)

Participants will receive doses of AMG 193 and comparator AMG 193 test tables at different times in a fasted state.

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

AMG 193: Orally via tablet

Comparator AMG 193 Test Tablet

Intervention Type DRUG

Comparator AMG 193 test tablet: Orally via tablet. Only participants in the DSPS group of the Part 1a, Phase 1: AMG 193 Monotherapy Dose Exploration, and Part 1j, Phase 1 arms will receive comparator AMG 193 test tablet.

Part 1k, Phase 1: AMG 193 Food Effect Substudy (US Sites Only)

Participants will receive AMG 193 once on a fasted state and once after eating a standardized high-fat, high calorie meal.

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

AMG 193: Orally via tablet

Part 1l, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null esophageal/gastric cancer.

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

AMG 193: Orally via tablet

Part 1m, Phase 1: AMG 193 Monotherapy Dose Expansion

Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null glioma.

Group Type EXPERIMENTAL

AMG 193

Intervention Type DRUG

AMG 193: Orally via tablet

Interventions

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AMG 193

AMG 193: Orally via tablet

Intervention Type DRUG

Docetaxel

Docetaxel: Intravenous infusion

Intervention Type DRUG

Comparator AMG 193 Test Tablet

Comparator AMG 193 test tablet: Orally via tablet. Only participants in the DSPS group of the Part 1a, Phase 1: AMG 193 Monotherapy Dose Exploration, and Part 1j, Phase 1 arms will receive comparator AMG 193 test tablet.

Intervention Type DRUG

Other Intervention Names

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MTA Cooperative PRMT5 inhibitor

Eligibility Criteria

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Inclusion Criteria

* Participant has provided informed consent/assent before initiation of any study specific activities/procedures.
* Age ≥ 18 years.
* Evidence of homozygous loss of cyclin dependent kinase inhibitor 2A (CDKN2A) (null) (Parts 1a, 1j, 1k, and 2a only) and/or methylthioadenosine phosphorylase (MTAP) (null) in the tumor tissue or blood (Parts 1a to 1k, Parts 2a and 2b) or lost MTAP expression in the tumor tissue (Parts 1a to 1k, Parts 2a and 2b).
* Histologically confirmed metastatic or locally advanced solid tumor not amenable to curative treatment with surgery and/or radiation.
* Able to swallow and retain orally (PO) administered study treatment and willing to record daily adherence to investigational product.
* Disease measurable as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Note: except participants enrolling to Part 1m.
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
* Adequate hematopoietic function per local laboratory
* Adequate renal function per local laboratory
* Adequate glucose control per local laboratory (Part 1 only)
* Adequate liver function per local laboratory
* Adequate coagulation parameters
* Adequate pulmonary function
* Adequate cardiac function
* Minimum life expectancy of 12 weeks as per investigator judgement.
* Archived tumor tissue (formalin-fixed, paraffin-embedded \[FFPE\] sample collected within 5 years) or an archival block must be available.
* For Part 1f (MTAP-null or lost MTAP expression HNSCC): Must be willing to undergo tumor biopsy.
* For Part 1a: Must be willing to undergo tumor biopsy, before start of treatment (archival sample acceptable if obtained with 6 months of enrollment and subject has not received any other treatment since sample was obtained) and while on treatment.
* For DSPS study (Part 1j): Must be willing to participate in DSPS substudy (US sites only).


* Subject able and willing to eat a standardized high-fat, high-caloric meal
* Subject able and willing to fast for ≥ 6 hours


\- Disease measurable as defined per Modified Response Assessment in Neuro-Oncology Criteria 2.0 (mRANO 2.0)

Exclusion Criteria

* Spinal cord compression or untreated brain metastases or leptomeningeal disease.
* History of other malignancy within the past 2 years
* Any evidence of current interstitial lung disease
* Active infection
* Evidence of active severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infection.
* History of arterial thrombosis
* Myocardial infarction and/or symptomatic congestive heart failure.
* Gastrointestinal tract disease
* History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
* History of solid organ transplant.
* Diagnosis of Congenital Short QT Syndrome.
* Major surgery
* Anti-tumor therapy within 28 days of study day 1.
* Prior treatment with an methionine adenosyltransferase 2α (MAT2A) inhibitor or a protein arginine methyltransferase 5 (PRMT5) inhibitor.
* Prior treatment with docetaxel (Part 2 only)
* Prior irradiation to 25% of the bone marrow.
* Therapeutic or palliative radiation therapy within 2 weeks of study day 1.
* Live vaccine therapy within 4 weeks before study drug administration.
* Use of therapeutic anti-coagulation for treatment of active thromboembolic events.
* Use of prescription medications that are known strong inducers of cytochrome P450 3A4 (CYP3A4) within 14 days or 5 half-lives (whichever is longer) before study day 1
* Unresolved toxicity from prior anti-cancer therapy
* Currently receiving treatment in another investigational device or drug study.
* Known positive test for Human Immunodeficiency Virus (HIV).
* Positive hepatitis B surface antigen
* positive hepatitis C virus ribonucleic acid (RNA) by polymerase chain reaction (PCR)
* Female participants of childbearing potential unwilling to use protocol specified method of contraception
Minimum Eligible Age

18 Years

Maximum Eligible Age

100 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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City of Hope National Medical Center

Duarte, California, United States

Site Status RECRUITING

California Research Institute

Glendale, California, United States

Site Status TERMINATED

Fomat Medical Research

Oxnard, California, United States

Site Status TERMINATED

University of California at SF

San Francisco, California, United States

Site Status RECRUITING

D and H Cancer Research Center

Margate, Florida, United States

Site Status TERMINATED

Boca Raton Clinical Research Medical Center Inc

Tamarac, Florida, United States

Site Status TERMINATED

Goshen Health Systems

Goshen, Indiana, United States

Site Status TERMINATED

Indiana University

Indianapolis, Indiana, United States

Site Status TERMINATED

Community Health Network MD Anderson Cancer Center - North

Indianapolis, Indiana, United States

Site Status RECRUITING

University of Maryland Medical Center

Baltimore, Maryland, United States

Site Status RECRUITING

American Oncology Partners, PA

Bethesda, Maryland, United States

Site Status TERMINATED

Henry Ford Cancer Detroit (Brigitte Harris Cancer Pavilion)

Detroit, Michigan, United States

Site Status RECRUITING

Washington University

St Louis, Missouri, United States

Site Status RECRUITING

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, United States

Site Status RECRUITING

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status RECRUITING

Northwell Health Monter Cancer Center

Lake Success, New York, United States

Site Status RECRUITING

New York University Grossman School of Medicine and New York University Langone Hospitals

New York, New York, United States

Site Status RECRUITING

Duke University

Durham, North Carolina, United States

Site Status RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

Site Status RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Sanford Oncology Clinic and Pharmacy

Sioux Falls, South Dakota, United States

Site Status RECRUITING

Sarah Cannon Research Institute

Dallas, Texas, United States

Site Status RECRUITING

Center for Oncology and Blood Disorders

Houston, Texas, United States

Site Status TERMINATED

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Lumi Research

Kingwood, Texas, United States

Site Status RECRUITING

South Texas Accelerated Research Therapeutics

San Antonio, Texas, United States

Site Status RECRUITING

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Site Status RECRUITING

Virginia Cancer Specialists PC

Fairfax, Virginia, United States

Site Status RECRUITING

Chris OBrien Lifehouse

Camperdown, New South Wales, Australia

Site Status RECRUITING

Epworth Healthcare

East Melbourne, Victoria, Australia

Site Status RECRUITING

Peter MacCallum Cancer Centre

Parkville, Victoria, Australia

Site Status RECRUITING

Medizinische Universitaet Graz

Graz, , Austria

Site Status RECRUITING

Landeskrankenhaus Salzburg

Salzburg, , Austria

Site Status RECRUITING

Universite Catholique de Louvain Cliniques Universitaires Saint Luc

Brussels, , Belgium

Site Status RECRUITING

Universitair Ziekenhuis Antwerpen

Edegem, , Belgium

Site Status RECRUITING

Universitair Ziekenhuis Gent

Ghent, , Belgium

Site Status RECRUITING

Jessa Ziekenhuis - Campus Virga Jesse

Hasselt, , Belgium

Site Status RECRUITING

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, , Belgium

Site Status RECRUITING

Cross Cancer Institute

Edmonton, Alberta, Canada

Site Status RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status RECRUITING

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, China

Site Status RECRUITING

Fujian Cancer Hospital

Fuzhou, Fujian, China

Site Status RECRUITING

Mengchao Hepatobiliary Hospital of Fujian Medical University

Fuzhou, Fujian, China

Site Status RECRUITING

Shanghai East Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Centre Georges Francois Leclerc

Dijon, , France

Site Status RECRUITING

Centre Oscar Lambret

Lille, , France

Site Status RECRUITING

Hopitaux Universitaires Pitie Salpetriere - Charles Foix

Paris, , France

Site Status RECRUITING

Gustave Roussy

Villejuif, , France

Site Status RECRUITING

Universitaetsklinikum Halle - Saale

Halle, , Germany

Site Status COMPLETED

Universitaetsklinikum Heidelberg

Heidelberg, , Germany

Site Status RECRUITING

Universitaetsklinikum Ulm

Ulm, , Germany

Site Status COMPLETED

Universitaetsklinikum Wuerzburg

Würzburg, , Germany

Site Status RECRUITING

Queen Mary Hospital, The University of Hong Kong

Hong Kong, , Hong Kong

Site Status RECRUITING

Prince of Wales Hospital, Chinese University of Hong Kong

Shatin, New Territories, , Hong Kong

Site Status RECRUITING

Aichi Cancer Center

Nagoya, Aichi-ken, Japan

Site Status RECRUITING

National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan

Site Status RECRUITING

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

Site Status RECRUITING

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, , South Korea

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Severance Hospital Yonsei University Health System

Seoul, , South Korea

Site Status RECRUITING

Asan Medical Center

Seoul, , South Korea

Site Status RECRUITING

Istituto Oncologico della Svizzera Italiana

Bellinzona, , Switzerland

Site Status RECRUITING

Inselspital Bern

Bern, , Switzerland

Site Status RECRUITING

Hopitaux Universitaires de Geneve

Geneva, , Switzerland

Site Status RECRUITING

Kantonsspital Sankt Gallen

Sankt Gallen, , Switzerland

Site Status RECRUITING

Universitaetsspital Zuerich

Zurich, , Switzerland

Site Status RECRUITING

National Cheng Kung University Hospital

Tainan, , Taiwan

Site Status RECRUITING

National Taiwan University Hospital

Taipei, , Taiwan

Site Status RECRUITING

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status RECRUITING

Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation

Taoyuan District, , Taiwan

Site Status TERMINATED

Sarah Cannon Research Institute UK

London, , United Kingdom

Site Status RECRUITING

Royal Marsden Hospital

Sutton, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Austria Belgium Canada China France Germany Hong Kong Japan South Korea Switzerland Taiwan United Kingdom

Central Contacts

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Amgen Call Center

Role: CONTACT

Phone: 866-572-6436

Email: [email protected]

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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2023-504363-17

Identifier Type: OTHER

Identifier Source: secondary_id

20210023

Identifier Type: -

Identifier Source: org_study_id