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

NCT06333951 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 20230167
• Study Type: interventional
• Target: 500
• Locations: 19 countries
• Sites: 81

Brief Summary

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.

Conditions

Thoracic Tumors; Non-small Cell Lung Cancer

Keywords

Oncology; Methylthioadenosine phosphorylase; AMG 193; PRMT5 inhibitor; MTAP; NSCLC

Outcome Measures

Primary Outcomes (3)

• Number of Participants Experiencing Dose Limiting Toxicities (DLT)

  Up to approximately 21 days

• Number of Participants Experiencing Treatment Emergent Adverse Events (TEAE)

  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)

  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 Outcomes (13)

• Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)

  Up to approximately 3 years

• Disease Control (DC) per RECIST v1.1

  Up to approximately 3 years

• Duration of Response (DOR) per RECIST v1.1

  Up to approximately 3 years

• Time to Response (TTR) per RECIST v1.1

  Up to approximately 3 years

• Overall Survival (OS) per RECIST v1.1

  Up to approximately 3 years

Study Arms (5)

Subprotocol A: Non-Small Cell Lung Cancer (NSCLC) Arm A

EXPERIMENTAL

Participants with MTAP-deleted NSCLC will receive a regimen of Anvumetostat orally (PO) and carboplatin, paclitaxel, and pembrolizumab intravenously (IV)

Drug: Anvumetostat; Drug: Carboplatin; Drug: Paclitaxel; Drug: Pembrolizumab

Subprotocol A: NSCLC Arm B

EXPERIMENTAL

Participants with MTAP-deleted NSCLC will receive a regimen of Anvumetostat PO and carboplatin, pemetrexed, and pembrolizumab IV

Drug: Anvumetostat; Drug: Carboplatin; Drug: Pembrolizumab; Drug: Pemetrexed

Subprotocol A: NSCLC Arm C

EXPERIMENTAL

Participants with MTAP-deleted NSCLC will receive a combination of Anvumetostat PO and pembrolizumab IV

Drug: Anvumetostat; Drug: Pembrolizumab

Subprotocol B: NSCLC With KRasG12C Mutation

EXPERIMENTAL

Participants with MTAP-deleted NSCLC and KRasG12C mutation will receive a combination of Anvumetostat and sotorasib PO

Drug: Anvumetostat; Drug: Sotorasib

Subprotocol C: NSCLC With Brain Metastases

EXPERIMENTAL

Participants with MTAP-deleted NSCLC with brain metastases will receive Anvumetostat PO

Drug: Anvumetostat

Interventions

Anvumetostat DRUG

Administered PO

Also known as: AMG 193

Subprotocol A: NSCLC Arm B; Subprotocol A: NSCLC Arm C; Subprotocol A: Non-Small Cell Lung Cancer (NSCLC) Arm A; Subprotocol B: NSCLC With KRasG12C Mutation; Subprotocol C: NSCLC With Brain Metastases

Carboplatin DRUG

Administered IV

Subprotocol A: NSCLC Arm B; Subprotocol A: Non-Small Cell Lung Cancer (NSCLC) Arm A

Sotorasib DRUG

Administered PO

Subprotocol B: NSCLC With KRasG12C Mutation

Paclitaxel DRUG

Administered IV

Subprotocol A: Non-Small Cell Lung Cancer (NSCLC) Arm A

Pembrolizumab DRUG

Administered IV

Subprotocol A: NSCLC Arm B; Subprotocol A: NSCLC Arm C; Subprotocol A: Non-Small Cell Lung Cancer (NSCLC) Arm A

Pemetrexed DRUG

Administered IV

Subprotocol A: NSCLC Arm B

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Subprotocol A, B, and C
• 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'

Sponsors & Collaborators

• Amgen: lead

Study Sites (83)

Comprehensive Blood and Cancer Center

Bakersfield, California, 93309, United States

RECRUITING

City of Hope National Medical Center

Duarte, California, 91010, United States

TERMINATED

City of Hope Orange County Lennar Foundation Cancer Center

Duarte, California, 91010, United States

TERMINATED

Translational Research in Oncology US Inc, Trio Central Pharmacy

Los Angeles, California, 90095, United States

RECRUITING

University of California Irvine

Orange, California, 92868-3217, United States

RECRUITING

University of California Los Angeles

Santa Monica, California, 90404, United States

RECRUITING

Rocky Mountain Cancer Centers

Denver, Colorado, 80218, United States

RECRUITING

Eastern Connecticut Hematology and Oncology Associates

Norwich, Connecticut, 06360, United States

TERMINATED

HealthPartners Institute

Saint Paul, Minnesota, 55102, United States

RECRUITING

Saint Lukes Hospital of Kansas City

Kansas City, Missouri, 64111, United States

TERMINATED

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

TERMINATED

Roswell Park Cancer Institute

Buffalo, New York, 32224, United States

RECRUITING

New York University Grossman School of Medicine

New York, New York, 10016, United States

RECRUITING

Perlmutter Cancer Center at New York University Langone Hospital----Long Island

New York, New York, 10016, United States

RECRUITING

Upstate University Hospital

Syracuse, New York, 13210, United States

RECRUITING

Hightower Clinical

Oklahoma City, Oklahoma, 73102, United States

RECRUITING

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

University of Tennessee Medical Center Knoxville

Knoxville, Tennessee, 37920, United States

RECRUITING

United States Oncology Regulatory Affairs Corporate Office

Nashville, Tennessee, 37203, United States

RECRUITING

Texas Oncology - Dallas Fort Worth

Dallas, Texas, 75246, United States

TERMINATED

US Oncology Research Investigational Products Center

Dallas, Texas, 75246, United States

RECRUITING

Oncology Consultants Cancer Center

Houston, Texas, 77030, United States

TERMINATED

Texas Oncology Northeast Texas

Tyler, Texas, 75702, United States

RECRUITING

Virginia Cancer Specialists PC

Fairfax, Virginia, 22031, United States

RECRUITING

Northwest Medical Specialties, PLLC

Tacoma, Washington, 98405, United States

RECRUITING

Instituto Argentino de Diagnóstico y Tratamiento

Ciudad Automona de Buenos Aires, Buenos Aires, C1117ABC, Argentina

RECRUITING

Hospital Universitario Austral

Pilar, Buenos Aires, B1629ODT, Argentina

RECRUITING

Cemic

Ciudad Autonoma Buenos Aires, C1431FWO, Argentina

RECRUITING

Orange Health Service

Orange, New South Wales, 2800, Australia

RECRUITING

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

RECRUITING

Medizinische Universitaet Graz

Graz, 8036, Austria

RECRUITING

Medizinische Universitaet Innsbruck

Innsbruck, 6020, Austria

RECRUITING

Centre Hospitalier Universitaire de Liege - Sart Tilman

Liège, 4000, Belgium

RECRUITING

Oncosite Centro de Pesquisa Clinica Em Oncologia Ltda

Ijuí, Rio Grande do Sul, 98700-000, Brazil

RECRUITING

Cipo - Centro Integrado de Pesquisa em Oncologia

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

RECRUITING

Fund Faculdade Regional Med Sao Jose Rio Preto

São José do Rio Preto, São Paulo, 15090-000, Brazil

RECRUITING

Beneficencia Portuguesa de Sao Paulo - Bp

São Paulo, São Paulo, 01509-900, Brazil

RECRUITING

Instituto Cancer Sao Paulo Icesp

São Paulo, 01246-000, Brazil

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

RECRUITING

Mengchao Hepatobiliary Hospital of Fujian Medical University

Fuzhou, Fujian, 350028, China

RECRUITING

Guangdong Provincial Peoples Hospital

Guangzhou, Guangdong, 510000, China

RECRUITING

The First Affiliated Hospital of Zhengzhou University

Zhengzhou, Henan, 450052, China

RECRUITING

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

RECRUITING

Jilin Cancer Hospital

Changchun, Jilin, 130012, China

RECRUITING

West China Hospital Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Beijing Cancer Hospital

Beijing, 100142, China

RECRUITING

Institut Bergonie

Bordeaux, 33000, France

RECRUITING

Hopital de la Timone

Marseille, 13005, France

RECRUITING

Institut de Cancerologie de l Ouest Rene Gauducheau

Saint-Herblain, 44805, France

RECRUITING

Gustave Roussy

Villejuif, 94805, France

RECRUITING

Universitaetsklinikum Essen

Essen, 45147, Germany

RECRUITING

Universitaetsklinikum Heidelberg

Heidelberg, 69126, Germany

RECRUITING

Universitaetsklinikum Wuerzburg

Würzburg, 97078, Germany

RECRUITING

Alexandra Hospital

Athens, 11528, Greece

RECRUITING

General Hospital Of Thessaloniki Papageorgiou

Thessaloniki, 56429, Greece

RECRUITING

European Interbalkan Medical Center

Thessaloniki, 57001, Greece

RECRUITING

Queen Mary Hospital, The University of Hong Kong

Hong Kong, Hong Kong

RECRUITING

Prince of Wales Hospital, Chinese University of Hong Kong

Shatin, New Territories, Hong Kong

RECRUITING

Fondazione IRCCS Istituto Nazionale dei Tumori

Alessandria, 15100, Italy

RECRUITING

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

RECRUITING

IRCCS Istituto Clinico Humanitas

Rozzano (MI), 20089, Italy

RECRUITING

Centro Ricerche Cliniche Di Verona Societa responsabilita limitata

Verona, 37126, Italy

RECRUITING

Aichi Cancer Center

Nagoya, Aichi-ken, 464-8681, Japan

RECRUITING

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

RECRUITING

Shizuoka Cancer Center

Sunto-gun, Shizuoka, 411-8777, Japan

RECRUITING

Wakayama Medical University Hospital

Wakayama, Wakayama, 641-8510, Japan

RECRUITING

Radboud Universitair Medisch Centrum

Nijmegen, 6525 GA, Netherlands

RECRUITING

Uniwersyteckie Centrum Kliniczne

Gdansk, 80-214, Poland

RECRUITING

Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie Panstwowy Instytut Badawczy

Gliwice, 44-102, Poland

RECRUITING

Futuremeds spolka z ograniczona odpowiedzialnoscia

Krakow, 31-501, Poland

RECRUITING

Instytut Centrum Zdrowia Matki Polki

Lodz, 93-338, Poland

RECRUITING

Centrum Medyczne Hope Clinic Sebastian Szklener

Lublin, 20-701, Poland

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Hospital Universitari Vall d Hebron

Barcelona, Catalonia, 08035, Spain

RECRUITING

Hospital Clinic i Provincial de Barcelona

Barcelona, Catalonia, 08036, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

RECRUITING

Adana Sehir Egitim ve Arastirma Hastanesi

Adana, 01370, Turkey (Türkiye)

RECRUITING

Hacettepe Universitesi Tip Fakultesi Hastanesi

Ankara, 06230, Turkey (Türkiye)

RECRUITING

Ankara Bilkent Sehir Hastanesi

Ankara, 06800, Turkey (Türkiye)

RECRUITING

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasms

Interventions

Carboplatin; Paclitaxel; pembrolizumab; Pemetrexed; sotorasib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Central Study Contacts

Amgen Call Center

CONTACT

866-572-6436; medinfo@amgen.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 21, 2024
• First Posted: March 27, 2024
• Study Start: September 17, 2024
• Primary Completion (Estimated): October 27, 2028
• Study Completion (Estimated): October 27, 2031
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

BE (1); HK (2); FR (4); NL (1); US (26); ES (3); AU (2); PL (5); GR (3); AR (3); BR (5); IT (4); TU (3); CA (1); JP (4); DE (3); TW (2); KR (2); CN (7)