A Study of Anvumetostat in Participants With Advanced MTAP-null Solid Tumors (MTAPESTRY 101)

NCT05094336 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 202100232023-504363-17
• Study Type: interventional
• Target: 329
• Locations: 13 countries
• Sites: 73

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 Anvumetostat 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 Anvumetostat in adult participants with metastatic or locally advanced MTAP-null solid tumors.

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

Outcome Measures

Primary Outcomes (3)

• Parts 1 and 2: Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)

  28 days

• Parts 1 and 2: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)

  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 event

  Up to approximately 3 years

• Part 3: Objective Response Rate (ORR)

  Up to approximately 3 years

Secondary Outcomes (26)

• Parts 1 and 2: Maximal Plasma Concentration (Cmax) of Anvumetostat

  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: Time to Achieve Maximal Plasma Concentration (Tmax) of Anvumetostat

  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: Area Under the Plasma Concentration Versus Time Curve (AUC) of Anvumetostat

  Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Part 1 Cycle = 28 days, Part 2 Cycle =21 days)

• 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)

Study Arms (14)

Part 1a, Phase 1: Anvumetostat Monotherapy Dose Exploration

EXPERIMENTAL

Participants with MTAP-null solid tumors will receive escalating doses of Anvumetostat to estimate the MTD and/or the RP2D.

Drug: Anvumetostat

Part 1c, Phase 1: Anvumetostat Monotherapy Dose Expansion

EXPERIMENTAL

Participants will receive the identified MTD/RP2D of Anvumetostat in the following cohort: MTAP-null NSCLC.

Drug: Anvumetostat

Part 2a, Phase 1: Anvumetostat Dose Exploration + Docetaxel

EXPERIMENTAL

Participants with MTAP-null NSCLC will receive escalating doses of Anvumetostat + a fixed dose of docetaxel to estimate the MTD/RP2D of the combination.

Drug: Anvumetostat; Drug: Docetaxel

Part 2b, Phase 1: Anvumetostat + Docetaxel Dose Expansion

EXPERIMENTAL

Participants with MTAP-null NSCLC will receive the identified MTD/RP2D of Anvumetostat + docetaxel.

Drug: Anvumetostat; Drug: Docetaxel

Part 3: Anvumetostat Phase 2

EXPERIMENTAL

Participants with MTAP-null solid tumors will receive Anvumetostat.

Drug: Anvumetostat

Part 1e, Phase 1: Anvumetostat Monotherapy Dose Expansion

EXPERIMENTAL

Participants will receive the identified selected dose/MTD of Anvumetostat in the following cohort: MTAP-null BTC.

Drug: Anvumetostat

Part 1f, Phase 1: Anvumetostat Monotherapy Dose Expansion

EXPERIMENTAL

Participants will receive the identified selected dose/MTD of Anvumetostat in the following cohort: MTAP-null head and neck squamous cell carcinoma (HNSCC).

Drug: Anvumetostat

Part 1g, Phase 1: Anvumetostat Monotherapy Dose Expansion

EXPERIMENTAL

Participants will receive the identified selected dose/MTD of Anvumetostat in the following cohort: MTAP-null pancreatic adenocarcinoma.

Drug: Anvumetostat

Part 1h, Phase 1: Anvumetostat Monotherapy Dose Expansion

EXPERIMENTAL

Participants will receive the identified selected dose/MTD of Anvumetostat in the following cohort: MTAP-null or lost MTAP expression solid tumors (other than lymphoma or primary brain tumor).

Drug: Anvumetostat

Part 1i, Phase 1: Anvumetostat Dose Optimization

EXPERIMENTAL

Participants will receive a randomized dose optimization evaluation of Anvumetostat.

Drug: Anvumetostat

Part 1j, Phase 1: Anvumetostat DSPS Substudy (US Sites Only)

EXPERIMENTAL

Participants will receive doses of Anvumetostat and comparator Anvumetostat test tables at different times in a fasted state.

Drug: Anvumetostat; Drug: Comparator Anvumetostat Test Tablet

Part 1k, Phase 1: Anvumetostat Food Effect Substudy (US Sites Only)

EXPERIMENTAL

Participants will receive Anvumetostat once on a fasted state and once after eating a standardized high-fat, high calorie meal.

Drug: Anvumetostat

Part 1l, Phase 1: Anvumetostat Monotherapy Dose Expansion

EXPERIMENTAL

Participants will receive the identified selected dose/MTD of Anvumetostat in the following cohort: MTAP-null esophageal/gastric cancer.

Drug: Anvumetostat

Part 1m, Phase 1: Anvumetostat Monotherapy Dose Expansion

EXPERIMENTAL

Participants will receive the identified selected dose/MTD of Anvumetostat in the following cohort: MTAP-null glioma.

Drug: Anvumetostat

Interventions

Anvumetostat DRUG

Anvumetostat: Orally via tablet

Also known as: MTA Cooperative PRMT5 inhibitor, AMG 193

Part 1a, Phase 1: Anvumetostat Monotherapy Dose Exploration; Part 1c, Phase 1: Anvumetostat Monotherapy Dose Expansion; Part 1e, Phase 1: Anvumetostat Monotherapy Dose Expansion; Part 1f, Phase 1: Anvumetostat Monotherapy Dose Expansion; Part 1g, Phase 1: Anvumetostat Monotherapy Dose Expansion; Part 1h, Phase 1: Anvumetostat Monotherapy Dose Expansion; Part 1i, Phase 1: Anvumetostat Dose Optimization; Part 1j, Phase 1: Anvumetostat DSPS Substudy (US Sites Only); Part 1k, Phase 1: Anvumetostat Food Effect Substudy (US Sites Only); Part 1l, Phase 1: Anvumetostat Monotherapy Dose Expansion; Part 1m, Phase 1: Anvumetostat Monotherapy Dose Expansion; Part 2a, Phase 1: Anvumetostat Dose Exploration + Docetaxel; Part 2b, Phase 1: Anvumetostat + Docetaxel Dose Expansion; Part 3: Anvumetostat Phase 2

Comparator Anvumetostat Test Tablet DRUG

Comparator Anvumetostat test tablet: Orally via tablet. Only participants in the DSPS group of the Part 1a, Phase 1: Anvumetostat Monotherapy Dose Exploration, and Part 1j, Phase 1 arms will receive comparator Anvumetostat test tablet.

Part 1j, Phase 1: Anvumetostat DSPS Substudy (US Sites Only)

Docetaxel DRUG

Docetaxel: Intravenous infusion

Part 2a, Phase 1: Anvumetostat Dose Exploration + Docetaxel; Part 2b, Phase 1: Anvumetostat + Docetaxel Dose Expansion

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Amgen: lead

Study Sites (75)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

California Research Institute

Glendale, California, 91204, United States

Location

Fomat Medical Research

Oxnard, California, 93030, United States

Location

University of California at SF

San Francisco, California, 94158, United States

Location

D and H Cancer Research Center

Margate, Florida, 33063, United States

Location

Boca Raton Clinical Research Medical Center Inc

Tamarac, Florida, 33321, United States

Location

Goshen Health Systems

Goshen, Indiana, 46526, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Community Health Network MD Anderson Cancer Center - North

Indianapolis, Indiana, 46250, United States

Location

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

American Oncology Partners, PA

Bethesda, Maryland, 20817, United States

Location

Henry Ford Cancer Detroit (Brigitte Harris Cancer Pavilion)

Detroit, Michigan, 48202, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 32224, United States

Location

Northwell Health Monter Cancer Center

Lake Success, New York, 11042, United States

Location

New York University Grossman School of Medicine and New York University Langone Hospitals

New York, New York, 10016, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19106, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Sanford Oncology Clinic and Pharmacy

Sioux Falls, South Dakota, 54104, United States

Location

Sarah Cannon Research Institute

Dallas, Texas, 75230, United States

Location

Center for Oncology and Blood Disorders

Houston, Texas, 77030, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Lumi Research

Kingwood, Texas, 77339, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

Virginia Cancer Specialists PC

Fairfax, Virginia, 22031, United States

Location

Chris OBrien Lifehouse

Camperdown, New South Wales, 2050, Australia

Location

Epworth Healthcare

East Melbourne, Victoria, 3002, Australia

Location

Peter MacCallum Cancer Centre

Parkville, Victoria, 3050, Australia

Location

Medizinische Universitaet Graz

Graz, 8036, Austria

Location

Landeskrankenhaus Salzburg

Salzburg, 5020, Austria

Location

Universite Catholique de Louvain Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Antwerpen

Edegem, 2650, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Jessa Ziekenhuis - Campus Virga Jesse

Hasselt, 3500, Belgium

Location

Universitair Ziekenhuis Leuven - Campus Gasthuisberg

Leuven, 3000, Belgium

Location

Cross Cancer Institute

Edmonton, Alberta, T6G 1Z2, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality, 400044, China

Location

Fujian Cancer Hospital

Fuzhou, Fujian, 350014, China

Location

Mengchao Hepatobiliary Hospital of Fujian Medical University

Fuzhou, Fujian, 350028, China

Location

Shanghai East Hospital

Shanghai, Shanghai Municipality, 200123, China

Location

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

Centre Georges Francois Leclerc

Dijon, 21000, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

Hopitaux Universitaires Pitie Salpetriere - Charles Foix

Paris, 75013, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Universitaetsklinikum Halle - Saale

Halle, 06120, Germany

Location

Universitaetsklinikum Heidelberg

Heidelberg, 69120, Germany

Location

Universitaetsklinikum Ulm

Ulm, 89081, Germany

Location

Universitaetsklinikum Wuerzburg

Würzburg, 97078, Germany

Location

Queen Mary Hospital, The University of Hong Kong

Hong Kong, Hong Kong

Location

Prince of Wales Hospital, Chinese University of Hong Kong

Shatin, New Territories, Hong Kong

Location

Aichi Cancer Center

Nagoya, Aichi-ken, 464-8681, Japan

Location

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

Location

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

Location

Seoul National University Bundang Hospital

Seongnam-si, Gyeonggi-do, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Istituto Oncologico della Svizzera Italiana

Bellinzona, 6500, Switzerland

Location

Inselspital Bern

Bern, 3010, Switzerland

Location

Hopitaux Universitaires de Geneve

Geneva, 1211, Switzerland

Location

Kantonsspital Sankt Gallen

Sankt Gallen, 9007, Switzerland

Location

Universitaetsspital Zuerich

Zurich, 8091, Switzerland

Location

National Cheng Kung University Hospital

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

Location

Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation

Taoyuan District, 33305, Taiwan

Location

Sarah Cannon Research Institute UK

London, W1G 6AD, United Kingdom

Location

Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

Location

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Biliary Tract Neoplasms; Squamous Cell Carcinoma of Head and Neck; Esophageal Neoplasms; Stomach Neoplasms; Glioma

Interventions

Docetaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Digestive System Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Gastrointestinal Neoplasms; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 14, 2021
• First Posted: October 26, 2021
• Study Start: February 1, 2022
• Primary Completion (Estimated): May 27, 2026
• Study Completion (Estimated): May 29, 2028
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.

Locations

BE (5); AU (3); CH (5); US (30); DE (4); HK (2); TW (4); FR (4); CN (5); JP (3); KR (4); GB (2); CA (2)