Clinical trial NCT05094336: A Study of AMG 193 in Participants With Advanced MTAP-null Solid Tumors (MTAPESTRY 101)
Official title: A Phase 1/1b/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 193 Alone and in Combination With Docetaxel in Subjects With Advanced MTAP-null Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced MTAP-null Solid Tumors
Keywords: Metastatic MTAP-null solid tumors
Advanced MTAP-null solid tumors
Non-small cell lung cancer
Biliary Tract Cancer (BTC)
Head and neck squamous cell carcinoma
Pancreatic adenocarcinoma
Esophageal cancer
Gastric cancer
Glioma
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2021-10-26
Enrollment: 649
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary objective of Parts 1 and 2 of this study is to evaluate the safety, tolerability, and to determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) of AMG 193 alone and in combination with docetaxel in adult participants with metastatic or locally advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors.

The primary objective of Part 3 of this study is to evaluate the efficacy of AMG 193 in adult participants with metastatic or locally advanced MTAP-null solid tumors.


Eligibility criteria: Inclusion Criteria:

* Participant has provided informed consent/assent before initiation of any study specific activities/procedures.
* Age ≥ 18 years.
* Evidence of homozygous loss of cyclin dependent kinase inhibitor 2A (CDKN2A) (null) (Parts 1a, 1j, 1k, and 2a only) and/or methylthioadenosine phosphorylase (MTAP) (null) in the tumor tissue or blood (Parts 1a to 1k, Parts 2a and 2b) or lost MTAP expression in the tumor tissue (Parts 1a to 1k, Parts 2a and 2b).
* Histologically confirmed metastatic or locally advanced solid tumor not amenable to curative treatment with surgery and/or radiation.
* Able to swallow and retain orally (PO) administered study treatment and willing to record daily adherence to investigational product.
* Disease measurable as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Note: except participants enrolling to Part 1m.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.

* Adequate hematopoietic function per local laboratory
* Adequate renal function per local laboratory
* Adequate glucose control per local laboratory (Part 1 only)
* Adequate liver function per local laboratory
* Adequate coagulation parameters
* Adequate pulmonary function
* Adequate cardiac function
* Minimum life expectancy of 12 weeks as per investigator judgement.
* Archived tumor tissue (formalin-fixed, paraffin-embedded \[FFPE\] sample collected within 5 years) or an archival block must be available.
* For Part 1f (MTAP-null or lost MTAP expression HNSCC): Must be willing to undergo tumor biopsy.
* For Part 1a: Must be willing to undergo tumor biopsy, before start of treatment (archival sample acceptable if obtained with 6 months of enrollment and subject has not received any other treatment since sample was obtained) and while on treatment.
* For DSPS study (Part 1j): Must be willing to participate in DSPS substudy (US sites only).

Food Effect Substudy (Part 1k): Specific Inclusion Criteria

* Subject able and willing to eat a standardized high-fat, high-caloric meal
* Subject able and willing to fast for ≥ 6 hours

Specific Inclusion Criteria for subjects with glioma (Part 1m only)

- Disease measurable as defined per Modified Response Assessment in Neuro-Oncology Criteria 2.0 (mRANO 2.0)

Exclusion Criteria:

* Spinal cord compression or untreated brain metastases or leptomeningeal disease.
* History of other malignancy within the past 2 years
* Any evidence of current interstitial lung disease
* Active infection
* Evidence of active severe acute respiratory syndrome coronavirus 2 (SARS-COV2) infection.
* History of arterial thrombosis
* Myocardial infarction and/or symptomatic congestive heart failure.
* Gastrointestinal tract disease
* History of bowel obstruction, abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
* History of solid organ transplant.
* Diagnosis of Congenital Short QT Syndrome.
* Major surgery
* Anti-tumor therapy within 28 days of study day 1.
* Prior treatment with an methionine adenosyltransferase 2α (MAT2A) inhibitor or a protein arginine methyltransferase 5 (PRMT5) inhibitor.
* Prior treatment with docetaxel (Part 2 only)
* Prior irradiation to 25% of the bone marrow.
* Therapeutic or palliative radiation therapy within 2 weeks of study day 1.
* Live vaccine therapy within 4 weeks before study drug administration.
* Use of therapeutic anti-coagulation for treatment of active thromboembolic events.
* Use of prescription medications that are known strong inducers of cytochrome P450 3A4 (CYP3A4) within 14 days or 5 half-lives (whichever is longer) before study day 1
* Unresolved toxicity from prior anti-cancer therapy
* Currently receiving treatment in another investigational device or drug study.
* Known positive test for Human Immunodeficiency Virus (HIV).
* Positive hepatitis B surface antigen
* positive hepatitis C virus ribonucleic acid (RNA) by polymerase chain reaction (PCR)
* Female participants of childbearing potential unwilling to use protocol specified method of contraception

Primary outcomes:
measure: Parts 1 and 2: Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)
timeFrame: 28 days
measure: Parts 1 and 2: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)
timeFrame: Up to approximately 2 years
measure: Part 3: Objective Response Rate (ORR)
timeFrame: Up to approximately 2 years
Secondary outcomes:
measure: Parts 1 and 2: Maximal Plasma Concentration (Cmax) of AMG 193
timeFrame: Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Part 1 Cycle = 28 days, Part 2 Cycle =21 days)
measure: Parts 1 and 2: Time to Achieve Maximal Plasma Concentration (Tmax) of AMG 193
timeFrame: Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Part 1 Cycle = 28 days, Part 2 Cycle =21 days)
measure: Parts 1 and 2: Area Under the Plasma Concentration Versus Time Curve (AUC) of AMG 193
timeFrame: Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Part 1 Cycle = 28 days, Part 2 Cycle =21 days)
measure: Part 2 Only: Maximal Plasma Concentration (Cmax) of Docetaxel
timeFrame: Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Cycle =21 days)
measure: Part 2 Only: Time to Achieve Maximal Plasma Concentration (Tmax) of Docetaxel
timeFrame: Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Cycle =21 days)
measure: Part 2 Only: Area Under the Plasma Concentration Versus Time Curve (AUC) of Docetaxel
timeFrame: Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Cycle =21 days)
measure: Parts 1 and 2: ORR
timeFrame: Up to approximately 2 years
measure: Parts 1, 2 and 3: Disease Control Rate (DCR)
timeFrame: Up to approximately 2 years
measure: Parts 1, 2 and 3: Duration of Response (DoR)
timeFrame: Up to approximately 2 years
measure: Parts 1, 2 and 3: Time to Response (TTR)
timeFrame: Up to approximately 2 years
measure: Parts 1, 2 and 3: Duration of Disease Control (DC)
timeFrame: Up to approximately 2 years
measure: Parts 1, 2 and 3: Progression-Free Survival (PFS)
timeFrame: Up to approximately 2 years
measure: Parts 1, 2 and 3: Overall Survival (OS)
timeFrame: Up to approximately 2 years
measure: Part 3 Only: Number of Participants Who Experience TEAE
timeFrame: Up to approximately 2 years
measure: Part 1a Only: Maximal Plasma Concentration (Cmax) of AMG 193
timeFrame: Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days)
measure: Part 1a Only: Time to Achieve Maximal Plasma Concentration (Tmax) of AMG 193
timeFrame: Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days)
measure: Part 1a Only: Area Under the Plasma Concentration Versus Time Curve (AUC) of AMG 193
timeFrame: Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days)
measure: Part 1a Only: Maximal Plasma Concentration (Cmax) of Comparator AMG 193 Test Tablet
timeFrame: Cycle 2 Day 2 to pre-dose on Cycle 2 Day 3 (Cycle = 28 days)
measure: Part 1a Only: Time to Achieve Maximal Plasma Concentration (Tmax) of Comparator AMG 193 Test Tablet
timeFrame: Cycle 2 Day 2 to pre-dose on Cycle 2 Day 3 (Cycle = 28 days)
measure: Part 1a Only: Area Under the Plasma Concentration Versus Time Curve (AUC) of Comparator AMG 193 Test Tablet
timeFrame: Cycle 2 Day 2 to pre-dose on Cycle 2 Day 3 (Cycle = 28 days)
measure: Part 1k Only: Cmax of AMG 193 during fasted state
timeFrame: Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days)
measure: Part 1k Only: Tmax of AMG 193 during fasted state
timeFrame: Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days)
measure: Part 1k Only: AUC of AMG 193 during fasted state
timeFrame: Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days)
measure: Part 1k Only: Cmax of AMG 193 during fed state
timeFrame: Cycle 2 day 2 pre-dose up to 24 hours post-dose (Cycle = 28 days)
measure: Part 1k Only: Tmax of AMG 193 during fed state
timeFrame: Cycle 2 day 2 pre-dose up to 24 hours post-dose (Cycle = 28 days)
measure: Part 1k Only: AUC of AMG 193 during fed state
timeFrame: Cycle 2 day 2 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Glendale
country: United States
facility: California Research Institute
state: California
city: Oxnard
country: United States
facility: Fomat Medical Research
state: California
city: San Francisco
country: United States
facility: University of California at SF
state: California
city: Margate
country: United States
facility: D and H Cancer Research Center
state: Florida
city: Tamarac
country: United States
facility: Boca Raton Clinical Research Medical Center Inc
state: Florida
city: Goshen
country: United States
facility: Goshen Health Systems
state: Indiana
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Indianapolis
country: United States
facility: Community Health Network MD Anderson Cancer Center - North
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland Medical Center
state: Maryland
city: Bethesda
country: United States
facility: American Oncology Partners, PA
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Cancer Detroit (Brigitte Harris Cancer Pavilion)
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of NJ
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: Lake Success
country: United States
facility: Northwell Health Monter Cancer Center
state: New York
city: New York
country: United States
facility: New York University Grossman School of Medicine and New York University Langone Hospitals
state: New York
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Sioux Falls
country: United States
facility: Sanford Oncology Clinic and Pharmacy
state: South Dakota
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Houston
country: United States
facility: Center for Oncology and Blood Disorders
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Kingwood
country: United States
facility: Lumi Research
state: Texas
city: San Antonio
country: United States
facility: South Texas Accelerated Research Therapeutics
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: Camperdown
country: Australia
facility: Chris OBrien Lifehouse
state: New South Wales
city: East Melbourne
country: Australia
facility: Epworth Healthcare
state: Victoria
city: Parkville
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Graz
country: Austria
facility: Medizinische Universitaet Graz
city: Salzburg
country: Austria
facility: Landeskrankenhaus Salzburg
city: Bruxelles
country: Belgium
facility: Universite Catholique de Louvain Cliniques Universitaires Saint Luc
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis - Campus Virga Jesse
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven - Campus Gasthuisberg
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Chongqing
country: China
facility: Chongqing University Cancer Hospital
state: Chongqing
city: Fuzhou
country: China
facility: Fujian Cancer Hospital
state: Fujian
city: Fuzhou
country: China
facility: Mengchao Hepatobiliary hospital of Fujian Medical University
state: Fujian
city: Shanghai
country: China
facility: Shanghai East Hospital
state: Shanghai
city: Shanghai
country: China
facility: Shanghai Pulmonary Hospital
state: Shanghai
city: Dijon
country: France
facility: Centre Georges Francois Leclerc
city: Lille
country: France
facility: Centre Oscar Lambret
city: Paris
country: France
facility: Hopitaux Universitaires Pitie Salpetriere - Charles Foix
city: Villejuif
country: France
facility: Gustave Roussy
city: Halle (Saale)
country: Germany
facility: Universitaetsklinikum Halle - Saale
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
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: Nagoya-shi
country: Japan
facility: Aichi Cancer Center
state: Aichi
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
state: Tokyo
city: Seongnam-si, Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Bellinzona
country: Switzerland
facility: Istituto Oncologico della Svizzera Italiana
city: Bern
country: Switzerland
facility: Inselspital Bern
city: Geneve 14
country: Switzerland
facility: Hopitaux Universitaires de Geneve
city: Sankt Gallen
country: Switzerland
facility: Kantonsspital Sankt Gallen
city: Zuerich
country: Switzerland
facility: Universitaetsspital Zuerich
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: Taoyuan
country: Taiwan
facility: Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: