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Anvumetostat Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol) (MTAPESTRY 104).
NCT06333951 · Amgen
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Official title
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)
About this study
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.
Eligibility criteria
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 design
Enrollment target: 500 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-09-17
Estimated completion: 2031-10-27
Last updated: 2026-04-13
Interventions
Drug: AnvumetostatDrug: CarboplatinDrug: PaclitaxelDrug: PembrolizumabDrug: PemetrexedDrug: Sotorasib
Primary outcomes
- • Number of Participants Experiencing Dose Limiting Toxicities (DLT) (Up to approximately 21 days)
- • Number of Participants Experiencing Treatment Emergent Adverse Events (TEAE) (Up to approximately 3 years)
- • Number of Participants Experiencing Serious Adverse Events (SAE) (Up to approximately 3 years)
Sponsor
Amgen · industry
Contacts & investigators
ContactAmgen Call Center · contact · medinfo@amgen.com · 866-572-6436
InvestigatorMD · study_director, Amgen
All locations (83)
Comprehensive Blood and Cancer CenterRecruiting
Bakersfield, California, United States
City of Hope National Medical CenterTerminated
Duarte, California, United States
City of Hope Orange County Lennar Foundation Cancer CenterTerminated
Duarte, California, United States
Translational Research in Oncology US Inc, Trio Central PharmacyRecruiting
Los Angeles, California, United States
University of California IrvineRecruiting
Orange, California, United States
University of California Los AngelesRecruiting
Santa Monica, California, United States
Rocky Mountain Cancer CentersRecruiting
Denver, Colorado, United States
Eastern Connecticut Hematology and Oncology AssociatesTerminated
Norwich, Connecticut, United States
HealthPartners InstituteRecruiting
Saint Paul, Minnesota, United States
Saint Lukes Hospital of Kansas CityTerminated
Kansas City, Missouri, United States
Comprehensive Cancer Centers of NevadaTerminated
Las Vegas, Nevada, United States
Roswell Park Cancer InstituteRecruiting
Buffalo, New York, United States
New York University Grossman School of MedicineRecruiting
New York, New York, United States
Perlmutter Cancer Center at New York University Langone Hospital----Long IslandRecruiting
New York, New York, United States
Upstate University HospitalRecruiting
Syracuse, New York, United States
Hightower ClinicalRecruiting
Oklahoma City, Oklahoma, United States
Fox Chase Cancer CenterRecruiting
Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical CenterRecruiting
Pittsburgh, Pennsylvania, United States
University of Tennessee Medical Center KnoxvilleRecruiting
Knoxville, Tennessee, United States
United States Oncology Regulatory Affairs Corporate OfficeRecruiting
Nashville, Tennessee, United States
Texas Oncology - Dallas Fort WorthTerminated
Dallas, Texas, United States
US Oncology Research Investigational Products CenterRecruiting
Dallas, Texas, United States
Oncology Consultants Cancer CenterTerminated
Houston, Texas, United States
Texas Oncology Northeast TexasRecruiting
Tyler, Texas, United States
Virginia Cancer Specialists PCRecruiting
Fairfax, Virginia, United States
Northwest Medical Specialties, PLLCRecruiting
Tacoma, Washington, United States
Instituto Argentino de Diagnóstico y TratamientoRecruiting
Ciudad Automona de Buenos Aires, Buenos Aires, Argentina
Hospital Universitario AustralRecruiting
Pilar, Buenos Aires, Argentina
CemicRecruiting
Ciudad Autonoma Buenos Aires, Argentina
Orange Health ServiceRecruiting
Orange, New South Wales, Australia
The Queen Elizabeth HospitalRecruiting
Woodville South, South Australia, Australia
Medizinische Universitaet GrazRecruiting
Graz, Austria
Medizinische Universitaet InnsbruckRecruiting
Innsbruck, Austria
Centre Hospitalier Universitaire de Liege - Sart TilmanRecruiting
Liège, Belgium
Oncosite Centro de Pesquisa Clinica Em Oncologia LtdaRecruiting
Ijuí, Rio Grande do Sul, Brazil
Cipo - Centro Integrado de Pesquisa em OncologiaRecruiting
Porto Alegre, Rio Grande do Sul, Brazil
Fund Faculdade Regional Med Sao Jose Rio PretoRecruiting
São José do Rio Preto, São Paulo, Brazil
Beneficencia Portuguesa de Sao Paulo - BpRecruiting
São Paulo, São Paulo, Brazil
Instituto Cancer Sao Paulo IcespRecruiting
São Paulo, Brazil
Princess Margaret Cancer CentreRecruiting
Toronto, Ontario, Canada
Mengchao Hepatobiliary Hospital of Fujian Medical UniversityRecruiting
Fuzhou, Fujian, China
Guangdong Provincial Peoples HospitalRecruiting
Guangzhou, Guangdong, China
The First Affiliated Hospital of Zhengzhou UniversityRecruiting
Zhengzhou, Henan, China
Union Hospital Tongji Medical College Huazhong University of Science and TechnologyRecruiting
Wuhan, Hubei, China
Jilin Cancer HospitalRecruiting
Changchun, Jilin, China
West China Hospital Sichuan UniversityRecruiting
Chengdu, Sichuan, China
Beijing Cancer HospitalRecruiting
Beijing, China
Institut BergonieRecruiting
Bordeaux, France
Hopital de la TimoneRecruiting
Marseille, France
Institut de Cancerologie de l Ouest Rene GauducheauRecruiting
Saint-Herblain, France
Gustave RoussyRecruiting
Villejuif, France
Universitaetsklinikum EssenRecruiting
Essen, Germany
Universitaetsklinikum HeidelbergRecruiting
Heidelberg, Germany
Universitaetsklinikum WuerzburgRecruiting
Würzburg, Germany
Alexandra HospitalRecruiting
Athens, Greece
General Hospital Of Thessaloniki PapageorgiouRecruiting
Thessaloniki, Greece
European Interbalkan Medical CenterRecruiting
Thessaloniki, Greece
Queen Mary Hospital, The University of Hong KongRecruiting
Hong Kong, Hong Kong
Prince of Wales Hospital, Chinese University of Hong KongRecruiting
Shatin, New Territories, Hong Kong
Fondazione IRCCS Istituto Nazionale dei TumoriRecruiting
Alessandria, Italy
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano NiguardaRecruiting
Milan, Italy
IRCCS Istituto Clinico HumanitasRecruiting
Rozzano (MI), Italy
Centro Ricerche Cliniche Di Verona Societa responsabilita limitataRecruiting
Verona, Italy
Aichi Cancer CenterRecruiting
Nagoya, Aichi-ken, Japan
National Cancer Center Hospital EastRecruiting
Kashiwa-shi, Chiba, Japan
Shizuoka Cancer CenterRecruiting
Sunto-gun, Shizuoka, Japan
Wakayama Medical University HospitalRecruiting
Wakayama, Wakayama, Japan
Radboud Universitair Medisch CentrumRecruiting
Nijmegen, Netherlands
Uniwersyteckie Centrum KliniczneRecruiting
Gdansk, Poland
Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie Panstwowy Instytut BadawczyRecruiting
Gliwice, Poland
Futuremeds spolka z ograniczona odpowiedzialnosciaRecruiting
Krakow, Poland
Instytut Centrum Zdrowia Matki PolkiRecruiting
Lodz, Poland
Centrum Medyczne Hope Clinic Sebastian SzklenerRecruiting
Lublin, Poland
Seoul National University HospitalRecruiting
Seoul, South Korea
Asan Medical CenterRecruiting
Seoul, South Korea
Hospital Universitari Vall d HebronRecruiting
Barcelona, Catalonia, Spain
Hospital Clinic i Provincial de BarcelonaRecruiting
Barcelona, Catalonia, Spain
Hospital Universitario 12 de OctubreRecruiting
Madrid, Spain
National Cheng Kung University HospitalRecruiting
Tainan, Taiwan
Taipei Veterans General HospitalRecruiting
Taipei, Taiwan
Adana Sehir Egitim ve Arastirma HastanesiRecruiting
Adana, Turkey (Türkiye)
Hacettepe Universitesi Tip Fakultesi HastanesiRecruiting
Ankara, Turkey (Türkiye)
Ankara Bilkent Sehir HastanesiRecruiting
Ankara, Turkey (Türkiye)