Clinical trial NCT06333951: AMG 193 Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol) (MTAPESTRY 104).
Official title: A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 193 Alone or in Combination With Other Therapies in Subjects With Advanced Thoracic Tumors With Homozygous MTAP-deletion (Master Protocol)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Thoracic Tumors
Non-small Cell Lung Cancer
Keywords: Oncology
Methylthioadenosine phosphorylase
AMG 193
PRMT5 inhibitor
MTAP
NSCLC
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2024-03-27
Enrollment: 500
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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 thoracic tumors. 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 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 AMG 193 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 (AMG 193 + carboplatin + paclitaxel + pembrolizumab):

- Predominantly squamous histology.

Arm B (AMG 193 + carboplatin + pemetrexed + pembrolizumab):

- Predominantly non-squamous histology.

Arm C (AMG 193 + 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 AMG 193.
* 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'

Primary outcomes:
measure: Number of Participants Experiencing Dose Limiting Toxicities (DLT)
timeFrame: Up to approximately 21 days
measure: Number of Participants Experiencing Treatment Emergent Adverse Events (TEAE)
timeFrame: Up to approximately 3 years
measure: Number of Participants Experiencing Serious Adverse Events (SAE)
timeFrame: Up to approximately 3 years
Secondary outcomes:
measure: Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
timeFrame: Up to approximately 3 years
measure: Disease Control (DC) per RECIST v1.1
timeFrame: Up to approximately 3 years
measure: Duration of Response (DOR) per RECIST v1.1
timeFrame: Up to approximately 3 years
measure: Time to Response (TTR) per RECIST v1.1
timeFrame: Up to approximately 3 years
measure: Overall Survival (OS) per RECIST v1.1
timeFrame: Up to approximately 3 years
measure: Progression-free Survival (PFS) per RECIST v1.1
timeFrame: Up to approximately 3 years
measure: Maximum Plasma Concentration (Cmax) of AMG 193
timeFrame: Up to Day 1 of Cycle 5 (one cycle = 21 days)
measure: Time to Maximum Plasma Concentration (tmax) of AMG 193
timeFrame: Up to Day 1 of Cycle 5 (one cycle = 21 days)
measure: Area Under the Plasma Concentration-time Curve (AUC) of AMG 193
timeFrame: Up to Day 1 of Cycle 5 (one cycle = 21 days)
measure: Intracranial objective response (IOR) per Response Assessment in Neuro Oncology Brain Metastases (RANO-BM )
timeFrame: Up to approximately 3 years
measure: Intracranial Disease Control (IDC) per RANO-BM
timeFrame: Up to approximately 3 years
measure: Intracranial Duration of Response (IDOR) per RANO-BM
timeFrame: Up to approximately 3 years
measure: Time to Intracranial Radiation Therapy per RANO-BM
timeFrame: Up to approximately 3 years
Other outcomes:
Locations:
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: Translational Research in Oncology US Inc, Trio Central Pharmacy
state: California
city: Orange
country: United States
facility: University of California Irvine
state: California
city: Santa Monica
country: United States
facility: University of California Los Angeles
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Norwich
country: United States
facility: Eastern Connecticut Hematology and Oncology Associates
state: Connecticut
city: Saint Paul
country: United States
facility: HealthPartners Institute
state: Minnesota
city: Kansas City
country: United States
facility: Saint Lukes Hospital of Kansas City
state: Missouri
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: New York
country: United States
facility: New York University Grossman School of Medicine
state: New York
city: New York
country: United States
facility: Perlmutter Cancer Center at New York University Langone Hospital----Long Island
state: New York
city: Oklahoma City
country: United States
facility: Hightower Clinical
state: Oklahoma
city: Knoxville
country: United States
facility: University of Tennessee Medical Center Knoxville
state: Tennessee
city: Nashville
country: United States
facility: United States Oncology Regulatory Affairs Corporate Office
state: Tennessee
city: Dallas
country: United States
facility: Texas Oncology - Dallas Fort Worth
state: Texas
city: Dallas
country: United States
facility: US Oncology Research Investigational Products Center
state: Texas
city: Houston
country: United States
facility: Oncology Consultants Cancer Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology Northeast Texas
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists PC
state: Virginia
city: Tacoma
country: United States
facility: Northwest Medical Specialties, PLLC
state: Washington
city: Orange
country: Australia
facility: Orange Health Service
state: New South Wales
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Graz
country: Austria
facility: Medizinische Universitaet Graz
city: Innsbruck
country: Austria
facility: Medizinische Universitaet Innsbruck
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liege - Sart Tilman
city: Ijui
country: Brazil
facility: Oncosite Centro de Pesquisa Clinica Em Oncologia Ltda
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo Octavio Frias de Oliveira Icesp
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Fuzhou
country: China
facility: Mengchao Hepatobiliary hospital of Fujian Medical University
state: Fujian
city: Guangzhou
country: China
facility: Guangdong Provincial Peoples Hospital
state: Guangdong
city: Zhengzhou
country: China
facility: The First Affiliated Hospital of Zhengzhou University
state: Henan
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Changchun
country: China
facility: Jilin Cancer Hospital
state: Jilin
city: Beijing
country: China
facility: Beijing Cancer Hospital
city: Bordeaux
country: France
facility: Institut Bergonie
city: Marseille
country: France
facility: Hopital de la Timone
city: Saint Herblain
country: France
facility: Institut de Cancerologie de l Ouest Rene Gauducheau
city: Villejuif
country: France
facility: Gustave Roussy
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Athens
country: Greece
facility: Alexandra Hospital
city: Thessaloniki
country: Greece
facility: Saint Luke Hospital
city: Thessaloniki
country: Greece
facility: General Hospital Of Thessaloniki Papageorgiou
city: Hong Kong
country: Hong Kong
facility: Queen Mary Hospital, The University of Hong Kong
city: Shatin, New Territories
country: Hong Kong
facility: Prince of Wales Hospital, Chinese University of Hong Kong
city: Alessandria
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei Tumori
city: Milano
country: Italy
facility: Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
city: Rozzano (MI)
country: Italy
facility: IRCCS Istituto Clinico Humanitas
city: Verona
country: Italy
facility: Centro Ricerche Cliniche Di Verona Societa responsabilita limitata
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center
state: Aichi
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Wakayama-shi
country: Japan
facility: Wakayama Medical University Hospital
state: Wakayama
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Gliwice
country: Poland
facility: Narodowy Instytut Onkologii im Marii Slodowskiej Curie Panstwowy Instytut Badawczy
city: Kraków
country: Poland
facility: Futuremeds Spolka z Ograniczona Odpowiedzialnoscia
city: Lodz
country: Poland
facility: Instytut Centrum Zdrowia Matki Polki
city: Lublin
country: Poland
facility: Centrum Medyczne Hope Clinic Sebastian Szklener
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
state: Cataluña
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Adana
country: Turkey
facility: Adana Sehir Egitim ve Arastirma Hastanesi
city: Ankara
country: Turkey
facility: Ankara Bilkent Sehir Hastanesi
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: