A Study of AMG 193 in Participants With Advanced MTAP-null Solid Tumors (MTAPESTRY 101)
- Conditions
- Advanced MTAP-null Solid Tumors
- Interventions
- Registration Number
- NCT05094336
- Lead Sponsor
- Amgen
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 649
- 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)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 1a, Phase 1: AMG 193 Monotherapy Dose Exploration AMG 193 Participants with MTAP-null solid tumors will receive escalating doses of AMG 193 to estimate the MTD and/or the RP2D. Part 1c, Phase 1: AMG 193 Monotherapy Dose Expansion AMG 193 Participants will receive the identified MTD/RP2D of AMG 193 in the following cohort: MTAP-null NSCLC. Part 2a, Phase 1: AMG 193 Dose Exploration + Docetaxel AMG 193 Participants with MTAP-null NSCLC will receive escalating doses of AMG 193 + a fixed dose of docetaxel to estimate the MTD/RP2D of the combination. Part 2a, Phase 1: AMG 193 Dose Exploration + Docetaxel Docetaxel Participants with MTAP-null NSCLC will receive escalating doses of AMG 193 + a fixed dose of docetaxel to estimate the MTD/RP2D of the combination. Part 2b, Phase 1: AMG 193 + Docetaxel Dose Expansion AMG 193 Participants with MTAP-null NSCLC will receive the identified MTD/RP2D of AMG 193 + docetaxel. Part 2b, Phase 1: AMG 193 + Docetaxel Dose Expansion Docetaxel Participants with MTAP-null NSCLC will receive the identified MTD/RP2D of AMG 193 + docetaxel. Part 3: AMG 193 Phase 2 AMG 193 Participants with MTAP-null solid tumors will receive AMG 193. Part 1e, Phase 1: AMG 193 Monotherapy Dose Expansion AMG 193 Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null BTC. Part 1f, Phase 1: AMG 193 Monotherapy Dose Expansion AMG 193 Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null head and neck squamous cell carcinoma (HNSCC). Part 1g, Phase 1: AMG 193 Monotherapy Dose Expansion AMG 193 Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null pancreatic adenocarcinoma. Part 1h, Phase 1: AMG 193 Monotherapy Dose Expansion AMG 193 Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null or lost MTAP expression solid tumors (other than lymphoma or primary brain tumor). Part 1i, Phase 1: AMG 193 Dose Optimization AMG 193 Participants will receive a randomized dose optimization evaluation of AMG 193. Part 1j, Phase 1: AMG 193 DSPS Substudy (US Sites Only) AMG 193 Participants will receive doses of AMG 193 and comparator AMG 193 test tables at different times in a fasted state. Part 1j, Phase 1: AMG 193 DSPS Substudy (US Sites Only) Comparator AMG 193 Test Tablet Participants will receive doses of AMG 193 and comparator AMG 193 test tables at different times in a fasted state. Part 1k, Phase 1: AMG 193 Food Effect Substudy (US Sites Only) AMG 193 Participants will receive AMG 193 once on a fasted state and once after eating a standardized high-fat, high calorie meal. Part 1l, Phase 1: AMG 193 Monotherapy Dose Expansion AMG 193 Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null esophageal/gastric cancer. Part 1m, Phase 1: AMG 193 Monotherapy Dose Expansion AMG 193 Participants will receive the identified selected dose/MTD of AMG 193 in the following cohort: MTAP-null glioma.
- Primary Outcome Measures
Name Time Method Parts 1 and 2: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE) Up to approximately 2 years Adverse events (AEs) are defined as any untoward medical occurrence in clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in vital signs, electrocardiograms (ECGs) and clinical laboratory tests will be recorded as TEAEs.
Serious AEs (SAEs) are defined as any event that meets at least 1 of the following serious criteria:
* Results in death (fatal)
* Requires in-patient hospitalization or prolongation of existing hospitalization
* Results in persistent or significant disability/incapacity
* Is a congenital anomaly/birth defect
* Other medically important serious eventParts 1 and 2: Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) 28 days Part 3: Objective Response Rate (ORR) Up to approximately 2 years
- Secondary Outcome Measures
Name Time Method Part 2 Only: Maximal Plasma Concentration (Cmax) of Docetaxel Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Cycle =21 days) Part 2 Only: Time to Achieve Maximal Plasma Concentration (Tmax) of Docetaxel Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Cycle =21 days) Part 2 Only: Area Under the Plasma Concentration Versus Time Curve (AUC) of Docetaxel Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Cycle =21 days) Part 1a Only: Time to Achieve Maximal Plasma Concentration (Tmax) of AMG 193 Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days) Parts 1 and 2: Maximal Plasma Concentration (Cmax) of AMG 193 Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Part 1 Cycle = 28 days, Part 2 Cycle =21 days) Parts 1, 2 and 3: Progression-Free Survival (PFS) Up to approximately 2 years Part 1k Only: Cmax of AMG 193 during fasted state Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days) Part 1k Only: Tmax of AMG 193 during fasted state Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days) Part 1k Only: AUC of AMG 193 during fasted state Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days) Parts 1, 2 and 3: Time to Response (TTR) Up to approximately 2 years Parts 1 and 2: Area Under the Plasma Concentration Versus Time Curve (AUC) of AMG 193 Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Part 1 Cycle = 28 days, Part 2 Cycle =21 days) Parts 1, 2 and 3: Duration of Response (DoR) Up to approximately 2 years Parts 1, 2 and 3: Duration of Disease Control (DC) Up to approximately 2 years Part 3 Only: Number of Participants Who Experience TEAE Up to approximately 2 years AEs are defined as any untoward medical occurrence in clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in vital signs, ECGs and clinical laboratory tests will be recorded as TEAEs.
SAEs are defined as any event that meets at least 1 of the following serious criteria:
* Results in death (fatal)
* Requires in-patient hospitalization or prolongation of existing hospitalization
* Results in persistent or significant disability/incapacity
* Is a congenital anomaly/birth defect
* Other medically important serious eventPart 1a Only: Maximal Plasma Concentration (Cmax) of AMG 193 Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days) Parts 1 and 2: Time to Achieve Maximal Plasma Concentration (Tmax) of AMG 193 Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Part 1 Cycle = 28 days, Part 2 Cycle =21 days) Parts 1 and 2: ORR Up to approximately 2 years Parts 1, 2 and 3: Disease Control Rate (DCR) Up to approximately 2 years Parts 1, 2 and 3: Overall Survival (OS) Up to approximately 2 years Part 1a Only: Area Under the Plasma Concentration Versus Time Curve (AUC) of AMG 193 Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days) Part 1a Only: Maximal Plasma Concentration (Cmax) of Comparator AMG 193 Test Tablet Cycle 2 Day 2 to pre-dose on Cycle 2 Day 3 (Cycle = 28 days) Part 1a Only: Time to Achieve Maximal Plasma Concentration (Tmax) of Comparator AMG 193 Test Tablet Cycle 2 Day 2 to pre-dose on Cycle 2 Day 3 (Cycle = 28 days) Part 1a Only: Area Under the Plasma Concentration Versus Time Curve (AUC) of Comparator AMG 193 Test Tablet Cycle 2 Day 2 to pre-dose on Cycle 2 Day 3 (Cycle = 28 days) Part 1k Only: Cmax of AMG 193 during fed state Cycle 2 day 2 pre-dose up to 24 hours post-dose (Cycle = 28 days) Part 1k Only: AUC of AMG 193 during fed state Cycle 2 day 2 pre-dose up to 24 hours post-dose (Cycle = 28 days) Part 1k Only: Tmax of AMG 193 during fed state Cycle 2 day 2 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Trial Locations
- Locations (74)
City of Hope National Medical Center
🇺🇸Duarte, California, United States
California Research Institute
🇺🇸Glendale, California, United States
Fomat Medical Research
🇺🇸Oxnard, California, United States
University of California at SF
🇺🇸San Francisco, California, United States
D and H Cancer Research Center
🇺🇸Margate, Florida, United States
Boca Raton Clinical Research Medical Center Inc
🇺🇸Tamarac, Florida, United States
Goshen Health Systems
🇺🇸Goshen, Indiana, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Community Health Network MD Anderson Cancer Center - North
🇺🇸Indianapolis, Indiana, United States
University of Maryland Medical Center
🇺🇸Baltimore, Maryland, United States
American Oncology Partners, PA
🇺🇸Bethesda, Maryland, United States
Henry Ford Cancer Detroit (Brigitte Harris Cancer Pavilion)
🇺🇸Detroit, Michigan, United States
Washington University
🇺🇸Saint Louis, Missouri, United States
Rutgers Cancer Institute of NJ
🇺🇸New Brunswick, New Jersey, United States
Roswell Park Cancer Institute
🇺🇸Buffalo, New York, United States
Northwell Health Monter Cancer Center
🇺🇸Lake Success, New York, United States
New York University Grossman School of Medicine and New York University Langone Hospitals
🇺🇸New York, New York, United States
Duke University
🇺🇸Durham, North Carolina, United States
University Hospitals Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Thomas Jefferson University
🇺🇸Philadelphia, Pennsylvania, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
Sanford Oncology Clinic and Pharmacy
🇺🇸Sioux Falls, South Dakota, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
Center for Oncology and Blood Disorders
🇺🇸Houston, Texas, United States
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
Lumi Research
🇺🇸Kingwood, Texas, United States
South Texas Accelerated Research Therapeutics
🇺🇸San Antonio, Texas, United States
University of Virginia Cancer Center
🇺🇸Charlottesville, Virginia, United States
Virginia Cancer Specialists PC
🇺🇸Fairfax, Virginia, United States
Chris OBrien Lifehouse
🇦🇺Camperdown, New South Wales, Australia
Epworth Healthcare
🇦🇺East Melbourne, Victoria, Australia
Peter MacCallum Cancer Centre
🇦🇺Parkville, Victoria, Australia
Medizinische Universitaet Graz
🇦🇹Graz, Austria
Landeskrankenhaus Salzburg
🇦🇹Salzburg, Austria
Universite Catholique de Louvain Cliniques Universitaires Saint Luc
🇧🇪Bruxelles, Belgium
Universitair Ziekenhuis Antwerpen
🇧🇪Edegem, Belgium
Universitair Ziekenhuis Gent
🇧🇪Gent, Belgium
Jessa Ziekenhuis - Campus Virga Jesse
🇧🇪Hasselt, Belgium
Universitair Ziekenhuis Leuven - Campus Gasthuisberg
🇧🇪Leuven, Belgium
Cross Cancer Institute
🇨🇦Edmonton, Alberta, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Chongqing University Cancer Hospital
🇨🇳Chongqing, Chongqing, China
Fujian Cancer Hospital
🇨🇳Fuzhou, Fujian, China
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
Mengchao Hepatobiliary hospital of Fujian Medical University
🇨🇳Fuzhou, Fujian, China
Shanghai East Hospital
🇨🇳Shanghai, Shanghai, China
Shanghai Pulmonary Hospital
🇨🇳Shanghai, Shanghai, China
Centre Georges Francois Leclerc
🇫🇷Dijon, France
Centre Oscar Lambret
🇫🇷Lille, France
Gustave Roussy
🇫🇷Villejuif, France
Universitaetsklinikum Halle - Saale
🇩🇪Halle (Saale), Germany
Universitaetsklinikum Heidelberg
🇩🇪Heidelberg, Germany
Universitaetsklinikum Ulm
🇩🇪Ulm, Germany
Universitaetsklinikum Wuerzburg
🇩🇪Wuerzburg, Germany
Queen Mary Hospital, The University of Hong Kong
🇭🇰Hong Kong, Hong Kong
Prince of Wales Hospital, Chinese University of Hong Kong
🇭🇰Shatin, New Territories, Hong Kong
Aichi Cancer Center
🇯🇵Nagoya-shi, Aichi, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Chiba, Japan
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Istituto Oncologico della Svizzera Italiana
🇨🇭Bellinzona, Switzerland
Inselspital Bern
🇨🇭Bern, Switzerland
Hopitaux Universitaires de Geneve
🇨🇭Geneve 14, Switzerland
Kantonsspital St Gallen
🇨🇭Sankt Gallen, Switzerland
Universitaetsspital Zuerich
🇨🇭Zuerich, Switzerland
National Cheng Kung University Hospital
🇨🇳Tainan, Taiwan
Taipei Veterans General Hospital
🇨🇳Taipei, Taiwan
Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
🇨🇳Taoyuan, Taiwan
Sarah Cannon Research Institute UK
🇬🇧London, United Kingdom
Royal Marsden Hospital
🇬🇧Sutton, United Kingdom