Clinical trial NCT06360354: A Study Evaluating AMG 193 in Combination With Other Therapies in Participants With Advanced Gastrointestinal, Biliary Tract, or Pancreatic Cancers With Homozygous Methylthioadenosine Phosphorylase (MTAP)-Deletion
Official title: A Phase 1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 193 in Combination With Other Therapies in Subjects With Advanced Gastrointestinal, Biliary Tract, or Pancreatic Cancers With Homozygous MTAP-deletion
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Gastrointestinal, Biliary Tract, and Pancreatic Cancers
Keywords: Advanced Cancer
Methylthioadenosine Phosphorylase
AMG 193
Oncology
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2024-04-11
Enrollment: 188
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 gastrointestinal, biliary tract, or pancreatic cancers. 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 gastrointestinal, biliary tract, or pancreatic cancers.


Eligibility criteria: Subprotocol B

Inclusion:

* Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years).
* Histologically or cytologically confirmed diagnosis of metastatic and/or unresectable (locally advanced) adenocarcinoma of the pancreas.
* Tumor tissue (FFPE sample) or an archival block must be available. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before dosing.
* Homozygous MTAP-deletion.
* Disease measurable as defined by RECIST v1.1.
* Adequate organ function as defined in the protocol.

Exclusion:

* Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor.
* Radiation therapy within 28 days of first dose.
* Major surgery within 28 days of first dose of AMG 193.
* 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 transplantation.

Primary outcomes:
measure: Number of Participants Experiencing Dose Limiting Toxicities (DLT)
timeFrame: Up to 28 days
measure: Number of Participants Experiencing Treatment Emergent Adverse Events (TEAE)
timeFrame: Up to approximately 2 years
measure: Number of Participants Experiencing Serious Adverse Events (SAE)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST v1.1)
timeFrame: Up to approximately 2 years
measure: Disease Control (DC) per RECIST v1.1
timeFrame: Up to approximately 2 years
measure: Duration of Response (DOR) per RECIST v1.1
timeFrame: Up to approximately 2 years
measure: Time to Response (TTR) per RECIST v1.1
timeFrame: Up to approximately 2 years
measure: Overall Survival (OS) per RECIST v1.1
timeFrame: Up to approximately 2 years
measure: Progression-free Survival (PFS) per RECIST v1.1
timeFrame: Up to approximately 2 years
measure: Maximum Plasma Concentration (Cmax) of AMG193
timeFrame: Up to Day 1 of Cycle 5 (one cycle = 21 or 28 days)
measure: Time to Maximum Plasma Concentration (tmax) of AMG193
timeFrame: Up to Day 1 of Cycle 5 (one cycle = 21 or 28 days)
measure: Area Under the Plasma Concentration-time Curve (AUC) of AMG 193
timeFrame: Up to Day 1 of Cycle 5 (one cycle = 21 or 28 days)
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: La Jolla
country: United States
facility: University of California San Diego Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Translational Research in Oncology US Inc, Trio Central Pharmacy
state: California
city: Santa Monica
country: United States
facility: University of California Los Angeles
state: California
city: Aurora
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Norwalk
country: United States
facility: Norwalk Hospital
state: Connecticut
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Louisville
country: United States
facility: Norton Cancer Institute
state: Kentucky
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Omaha
country: United States
facility: University of Nebraska
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation
state: Ohio
city: Nashville
country: United States
facility: United States Oncology Regulatory Affairs Corporate Office
state: Tennessee
city: Houston
country: United States
facility: Oncology Consultants Cancer Center
state: Texas
city: Irving
country: United States
facility: US Oncology Research Investigational Products Center
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia Cancer Center
state: Virginia
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: Vancouver
country: United States
facility: Northwest Cancer Specialists - Vancouver
state: Washington
city: Camperdown
country: Australia
facility: Chris OBrien Lifehouse
state: New South Wales
city: St Leonards
country: Australia
facility: GenesisCare -North Shore Oncology
state: New South Wales
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Heidelberg
country: Australia
facility: Austin Health, Austin Hospital
state: Victoria
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: St Albans
country: Australia
facility: Epworth Healthcare
state: Victoria
city: Bruxelles
country: Belgium
facility: Universite Catholique de Louvain Cliniques Universitaires Saint Luc
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven - Campus Gasthuisberg
city: Calgary
country: Canada
facility: Arthur J E Child Comprehensive Cancer Centre
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Quebec
country: Canada
facility: CHU de Quebec Hopital de l Enfant Jesus
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
city: Wuhan
country: China
facility: Union Hospital Tongji Medical College Huazhong University of Science and Technology
state: Hubei
city: Herlev
country: Denmark
facility: Herlev og Gentofte Hospital
city: Bordeaux
country: France
facility: Institut Bergonie
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Marseille
country: France
facility: Institut Paoli Calmettes
city: Villejuif
country: France
facility: Gustave Roussy
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Heidelberg
country: Germany
facility: Universitaetsklinikum 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: Milano
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: Yokohama-shi
country: Japan
facility: Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center
state: Kanagawa
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Nijmegen
country: Netherlands
facility: Radboud Universitair Medisch Centrum
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
state: Andalucía
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
state: Cataluña
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Maranon
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Taipei Veterans General Hospital
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital Birmingham
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: