Anvumetostat Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol) (MTAPESTRY 104).

May 27, 2026 updated by: Amgen

A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Anvumetostat Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol)

The study aims to determine maximum tolerated dose (MTD) or recommended combination dose of the MTA-cooperative PRMT5 inhibitor Anvumetostat administered in combination with other therapies in adult participants with metastatic or locally advanced methylthioadenosine phosphorylase (MTAP)-deleted thoracic tumors. The study also aims to determine the safety profile of Anvumetostat administered in combination with other therapies in adult participants with metastatic or locally advanced MTAP-deleted thoracic tumors.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

49

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 Locations

  • Argentina
      • Ciudad Autonoma Buenos Aires, Argentina, C1431FWO
        • CEMIC
    • Buenos Aires
      • Ciudad Automona de Buenos Aires, Buenos Aires, Argentina, C1117ABC
        • Instituto Argentino de Diagnóstico y Tratamiento
      • Pilar, Buenos Aires, Argentina, B1629ODT
        • Hospital Universitario Austral
  • Australia
    • New South Wales
      • Orange, New South Wales, Australia, 2800
        • Orange Health Service
    • South Australia
      • Woodville South, South Australia, Australia, 5011
        • The Queen Elizabeth Hospital
  • Austria
      • Graz, Austria, 8036
        • Medizinische Universitaet Graz
      • Innsbruck, Austria, 6020
        • Medizinische Universitaet Innsbruck
  • Belgium
      • Liège, Belgium, 4000
        • Centre Hospitalier Universitaire de Liege - Sart Tilman
  • Brazil
      • São Paulo, Brazil, 01246-000
        • Instituto Cancer Sao Paulo Icesp
    • Rio Grande do Sul
      • Ijuí, Rio Grande do Sul, Brazil, 98700-000
        • Oncosite Centro de Pesquisa Clinica Em Oncologia Ltda
      • Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
        • Cipo - Centro Integrado de Pesquisa em Oncologia
    • São Paulo
      • São José do Rio Preto, São Paulo, Brazil, 15090-000
        • Fund Faculdade Regional Med Sao Jose Rio Preto
      • São Paulo, São Paulo, Brazil, 01509-900
        • Beneficencia Portuguesa de Sao Paulo - Bp
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Cancer Centre
  • China
      • Beijing, China, 100142
        • Beijing Cancer Hospital
    • Fujian
      • Fuzhou, Fujian, China, 350028
        • Mengchao Hepatobiliary Hospital of Fujian Medical University
    • Guangdong
      • Guangzhou, Guangdong, China, 510000
        • Guangdong Provincial Peoples Hospital
    • Henan
      • Zhengzhou, Henan, China, 450052
        • the First Affiliated Hospital of Zhengzhou University
    • Hubei
      • Wuhan, Hubei, China, 430022
        • Union Hospital Tongji Medical College Huazhong University of Science and Technology
    • Jilin
      • Changchun, Jilin, China, 130012
        • Jilin Cancer Hospital
    • Sichuan
      • Chengdu, Sichuan, China, 610041
        • West China Hospital Sichuan University
  • France
      • Bordeaux, France, 33000
        • Institut Bergonie
      • Marseille, France, 13005
        • Hopital de la Timone
      • Saint-Herblain, France, 44805
        • Institut de Cancerologie de l Ouest Rene Gauducheau
      • Villejuif, France, 94805
        • Gustave Roussy
  • Germany
      • Essen, Germany, 45147
        • Universitaetsklinikum Essen
      • Heidelberg, Germany, 69126
        • Universitaetsklinikum Heidelberg
      • Würzburg, Germany, 97078
        • Universitaetsklinikum Wuerzburg
  • Greece
      • Athens, Greece, 11528
        • Alexandra Hospital
      • Thessaloniki, Greece, 57001
        • European Interbalkan Medical Center
      • Thessaloniki, Greece, 56429
        • General Hospital Of Thessaloniki Papageorgiou
  • Hong Kong
      • Hong Kong, Hong Kong
        • Queen Mary Hospital, The University of Hong Kong
      • Shatin, New Territories, Hong Kong
        • Prince of Wales Hospital, Chinese University of Hong Kong
  • Italy
      • Alessandria, Italy, 15100
        • Fondazione IRCCS Istituto Nazionale dei Tumori
      • Milan, Italy, 20162
        • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
      • Rozzano (MI), Italy, 20089
        • IRCCS Istituto Clinico Humanitas
      • Verona, Italy, 37126
        • Centro Ricerche Cliniche Di Verona Societa responsabilita limitata
  • Japan
    • Aichi-ken
      • Nagoya, Aichi-ken, Japan, 464-8681
        • Aichi Cancer Center
    • Chiba
      • Kashiwa-shi, Chiba, Japan, 277-8577
        • National Cancer Center Hospital East
    • Shizuoka
      • Sunto-gun, Shizuoka, Japan, 411-8777
        • Shizuoka Cancer Center
    • Wakayama
      • Wakayama, Wakayama, Japan, 641-8510
        • Wakayama Medical University Hospital
  • Netherlands
      • Nijmegen, Netherlands, 6525 GA
        • Radboud Universitair Medisch Centrum
  • Poland
      • Gdansk, Poland, 80-214
        • Uniwersyteckie Centrum Kliniczne
      • Gliwice, Poland, 44-102
        • Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy
      • Krakow, Poland, 31-501
        • Futuremeds spolka z ograniczona odpowiedzialnoscia
      • Lodz, Poland, 93-338
        • Instytut Centrum Zdrowia Matki Polki
      • Lublin, Poland, 20-701
        • Centrum Medyczne Hope Clinic Sebastian Szklener
  • South Korea
      • Seoul, South Korea, 03080
        • Seoul National University Hospital
      • Seoul, South Korea, 05505
        • Asan Medical Center
  • Spain
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
    • Catalonia
      • Barcelona, Catalonia, Spain, 08036
        • Hospital Clínic i Provincial de Barcelona
      • Barcelona, Catalonia, Spain, 08035
        • Hospital Universitari Vall d Hebron
  • Taiwan
      • Tainan, Taiwan, 70403
        • National Cheng Kung University Hospital
      • Taipei, Taiwan, 11217
        • Taipei Veterans General Hospital
  • Turkey (Türkiye)
      • Adana, Turkey (Türkiye), 01370
        • Adana Sehir Egitim ve Arastirma Hastanesi
      • Ankara, Turkey (Türkiye), 06800
        • Ankara Bilkent Şehir Hastanesi
      • Ankara, Turkey (Türkiye), 06230
        • Hacettepe Universitesi Tip Fakultesi Hastanesi
  • United States
    • California
      • Bakersfield, California, United States, 93309
        • Comprehensive Blood and Cancer Center
      • Duarte, California, United States, 91010
        • City of Hope National Medical Center
      • Duarte, California, United States, 91010
        • City of Hope Orange County Lennar Foundation Cancer Center
      • Los Angeles, California, United States, 90095
        • Translational Research in Oncology US Inc, Trio Central Pharmacy
      • Orange, California, United States, 92868-3217
        • University of California Irvine
      • Santa Monica, California, United States, 90404
        • University of California Los Angeles
    • Colorado
      • Denver, Colorado, United States, 80218
        • Rocky Mountain Cancer Centers
    • Connecticut
      • Norwich, Connecticut, United States, 06360
        • Eastern Connecticut Hematology and Oncology Associates
    • Minnesota
      • Saint Paul, Minnesota, United States, 55102
        • HealthPartners Institute
    • Missouri
      • Kansas City, Missouri, United States, 64111
        • Saint Lukes Hospital of Kansas City
    • Nevada
      • Las Vegas, Nevada, United States, 89169
        • Comprehensive Cancer Centers of Nevada
    • New York
      • Buffalo, New York, United States, 32224
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10016
        • New York University Grossman School of Medicine
      • New York, New York, United States, 10016
        • Perlmutter Cancer Center at New York University Langone Hospital----Long Island
      • Syracuse, New York, United States, 13210
        • Upstate University Hospital
    • Oklahoma
      • Oklahoma City, Oklahoma, United States, 73102
        • Hightower Clinical
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Fox Chase Cancer Center
      • Pittsburgh, Pennsylvania, United States, 15232
        • University of Pittsburgh Medical Center
    • Tennessee
      • Knoxville, Tennessee, United States, 37920
        • University of Tennessee Medical Center Knoxville
      • Nashville, Tennessee, United States, 37203
        • United States Oncology Regulatory Affairs Corporate Office
    • Texas
      • Dallas, Texas, United States, 75246
        • Texas Oncology - Dallas Fort Worth
      • Dallas, Texas, United States, 75246
        • US Oncology Research Investigational Products Center
      • Houston, Texas, United States, 77030
        • Oncology Consultants Cancer Center
      • Tyler, Texas, United States, 75702
        • Texas Oncology Northeast Texas
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists PC
    • Washington
      • Tacoma, Washington, United States, 98405
        • NorthWest Medical Specialties, PLLC

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

Inclusion Criteria

Subprotocol A, B, and C

  • Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years).
  • Tumor tissue (formalin-fixed, paraffin-embedded sample) or an archival block must be available. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before Anvumetostat dosing.
  • Homozygous MTAP-deletion
  • Able to swallow and retain PO administered study treatment.
  • Disease measurable as defined by RECIST v1.1.

Subprotocol A - Histologically or cytologically confirmed diagnosis of NSCLC.

Arm A (Anvumetostat + carboplatin + paclitaxel + pembrolizumab):

- Predominantly squamous histology.

Arm B (Anvumetostat + carboplatin + pemetrexed + pembrolizumab):

- Predominantly non-squamous histology.

Arm C (Anvumetostat + pembrolizumab):

- PD-L1 positive.

Subprotocol B - Histologically confirmed NSCLC with homozygous MTAP-deletion and KRAS p.G12C mutation.

Subprotocol C

  • Histologically or cytologically confirmed diagnosis of NSCLC with brain metastases.
  • Brain lesion meeting RANO-BM criteria for measurable disease.

Exclusion Criteria

Subprotocol A, B, and C

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

Subprotocol A

- Autoimmune disease or immunodeficiency disease as defined in the protocol'

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: Non-Small Cell Lung Cancer (NSCLC) Arm A
Participants with MTAP-deleted NSCLC will receive a regimen of Anvumetostat orally (PO) and carboplatin, paclitaxel, and pembrolizumab intravenously (IV)
Drug: Pembrolizumab
Administered IV
Drug: Paclitaxel
Administered IV
Drug: Carboplatin
Administered IV
Drug: Anvumetostat
Administered PO
Other Names:
  • AMG 193
Experimental: Subprotocol A: NSCLC Arm B
Participants with MTAP-deleted NSCLC will receive a regimen of Anvumetostat PO and carboplatin, pemetrexed, and pembrolizumab IV
Drug: Pembrolizumab
Administered IV
Drug: Carboplatin
Administered IV
Drug: Pemetrexed
Administered IV
Drug: Anvumetostat
Administered PO
Other Names:
  • AMG 193
Experimental: Subprotocol A: NSCLC Arm C
Participants with MTAP-deleted NSCLC will receive a combination of Anvumetostat PO and pembrolizumab IV
Drug: Pembrolizumab
Administered IV
Drug: Anvumetostat
Administered PO
Other Names:
  • AMG 193
Experimental: Subprotocol B: NSCLC With KRasG12C Mutation
Participants with MTAP-deleted NSCLC and KRasG12C mutation will receive a combination of Anvumetostat and sotorasib PO
Drug: Sotorasib
Administered PO
Drug: Anvumetostat
Administered PO
Other Names:
  • AMG 193
Experimental: Subprotocol C: NSCLC With Brain Metastases
Participants with MTAP-deleted NSCLC with brain metastases will receive Anvumetostat PO
Drug: Anvumetostat
Administered PO
Other Names:
  • AMG 193

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 approximately 21 days
Up to approximately 21 days
Number of Participants Experiencing Treatment Emergent Adverse Events (TEAE)
Time Frame: Up to approximately 3 years
TEAEs are any event that occurred after the participant received study treatment. Any clinically significant changes in vital signs, electrocardiograms, and clinical laboratory tests that occurred after study treatment administration were recorded as TEAEs. A serious TEAE is any untoward medical occurrence in a clinical study participant after first dose irrespective of a causal relationship with the study treatment(s) that resulted in death, was immediately life threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, or another medically important serious event.
Up to approximately 3 years
Number of Participants Experiencing Serious Adverse Events (SAE)
Time Frame: Up to approximately 3 years
An SAE is defined as any AE that results in death, is life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital abnormality/birth defect or important medical events that do not meet the preceding criteria but based on appropriate medical judgment may jeopardize the participant or may require medical or surgical intervention to prevent any of the outcomes listed above.
Up to approximately 3 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 3 years
Up to approximately 3 years
Disease Control (DC) per RECIST v1.1
Time Frame: Up to approximately 3 years
Up to approximately 3 years
Duration of Response (DOR) per RECIST v1.1
Time Frame: Up to approximately 3 years
Up to approximately 3 years
Time to Response (TTR) per RECIST v1.1
Time Frame: Up to approximately 3 years
Up to approximately 3 years
Overall Survival (OS) per RECIST v1.1
Time Frame: Up to approximately 3 years
Up to approximately 3 years
Progression-free Survival (PFS) per RECIST v1.1
Time Frame: Up to approximately 3 years
Up to approximately 3 years
Intracranial objective response (IOR) per Response Assessment in Neuro Oncology Brain Metastases (RANO-BM )
Time Frame: Up to approximately 3 years
Up to approximately 3 years
Intracranial Disease Control (IDC) per RANO-BM
Time Frame: Up to approximately 3 years
Up to approximately 3 years
Intracranial Duration of Response (IDOR) per RANO-BM
Time Frame: Up to approximately 3 years
Up to approximately 3 years
Time to Intracranial Radiation Therapy per RANO-BM
Time Frame: Up to approximately 3 years
Up to approximately 3 years
Maximum Plasma Concentration (Cmax) of Anvumetostat
Time Frame: Up to Day 1 of Cycle 5 (one cycle = 21 days)
Up to Day 1 of Cycle 5 (one cycle = 21 days)
Time to Maximum Plasma Concentration (tmax) of Anvumetostat
Time Frame: Up to Day 1 of Cycle 5 (one cycle = 21 days)
Up to Day 1 of Cycle 5 (one cycle = 21 days)
Area Under the Plasma Concentration-time Curve (AUC) of Anvumetostat
Time Frame: Up to Day 1 of Cycle 5 (one cycle = 21 days)
Up to Day 1 of Cycle 5 (one cycle = 21 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 (Actual)

September 17, 2024

Primary Completion (Estimated)

October 31, 2026

Study Completion (Estimated)

November 30, 2026

Study Registration Dates

First Submitted

March 21, 2024

First Submitted That Met QC Criteria

March 21, 2024

First Posted (Actual)

March 27, 2024

Study Record Updates

Last Update Posted (Actual)

May 28, 2026

Last Update Submitted That Met QC Criteria

May 27, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20230167

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 reevaluating 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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