Advanced MTAP-null Solid TumorsPhase 1/2MTAPESTRY 101NCT05094336
A Study of Anvumetostat in Participants With Advanced MTAP-null Solid Tumors (MTAPESTRY 101)
A Phase 1/2 study testing Anvumetostat, Docetaxel and Comparator Anvumetostat Test Tablet in people with Advanced MTAP-null Solid Tumors, run by Amgen at 75 sites in 14 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Advanced MTAP-null Solid Tumors
- What is being tested?
- Anvumetostat, Docetaxel and Comparator Anvumetostat Test Tablet
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 329 participants
- Where
- 75 sitesin 14 countries
- Study dates
- 1 Feb 2022to 30 Nov 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 24Show fewer
- 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)
Who cannot join
- 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
Show all 26Show fewer
- 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
Trial locations and contacts
75 sites in 14 countries.
75 sites in 14 countries
United States30 sites
University of Maryland Medical Center
Baltimore, Maryland, 21201
American Oncology Partners, PA
Bethesda, Maryland, 20817
Roswell Park Cancer Institute
Buffalo, New York, 32224
University of Virginia Cancer Center
Charlottesville, Virginia, 22908
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Sarah Cannon Research Institute
Dallas, Texas, 75230
Henry Ford Cancer Detroit (Brigitte Harris Cancer Pavilion)
Detroit, Michigan, 48202
City of Hope National Medical Center
Duarte, California, 91010
Duke University
Durham, North Carolina, 27710
Virginia Cancer Specialists PC
Fairfax, Virginia, 22031
California Research Institute
Glendale, California, 91204
Goshen Health Systems
Goshen, Indiana, 46526
Center for Oncology and Blood Disorders
Houston, Texas, 77030
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
Community Health Network MD Anderson Cancer Center - North
Indianapolis, Indiana, 46250
Lumi Research
Kingwood, Texas, 77339
Northwell Health Monter Cancer Center
Lake Success, New York, 11042
D and H Cancer Research Center
Margate, Florida, 33063
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, 08903
New York University Grossman School of Medicine and New York University Langone Hospitals
New York, New York, 10016
Fomat Medical Research
Oxnard, California, 93030
University of Pennsylvania
Philadelphia, Pennsylvania, 19106
Thomas Jefferson University
Philadelphia, Pennsylvania, 19107
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15232
South Texas Accelerated Research Therapeutics
San Antonio, Texas, 78229
University of California at SF
San Francisco, California, 94158
Sanford Oncology Clinic and Pharmacy
Sioux Falls, South Dakota, 54104
Washington University
St Louis, Missouri, 63110
Boca Raton Clinical Research Medical Center Inc
Tamarac, Florida, 33321
Belgium5 sites
Universite Catholique de Louvain Cliniques Universitaires Saint Luc
Brussels, 1200
Universitair Ziekenhuis Antwerpen
Edegem, 2650
Universitair Ziekenhuis Gent
Ghent, 9000
Jessa Ziekenhuis - Campus Virga Jesse
Hasselt, 3500
Universitair Ziekenhuis Leuven - Campus Gasthuisberg
Leuven, 3000
China5 sites
Chongqing University Cancer Hospital
Chongqing, Chongqing Municipality, 400044
Fujian Cancer Hospital
Fuzhou, Fujian, 350014
Mengchao Hepatobiliary Hospital of Fujian Medical University
Fuzhou, Fujian, 350028
Shanghai East Hospital
Shanghai, Shanghai Municipality, 200123
Shanghai Pulmonary Hospital
Shanghai, Shanghai Municipality, 200433
Switzerland5 sites
Istituto Oncologico della Svizzera Italiana
Bellinzona, 6500
Inselspital Bern
Bern, 3010
Hopitaux Universitaires de Geneve
Geneva, 1211
Kantonsspital Sankt Gallen
Sankt Gallen, 9007
Universitaetsspital Zuerich
Zurich, 8091
France4 sites
Centre Georges Francois Leclerc
Dijon, 21000
Centre Oscar Lambret
Lille, 59020
Hopitaux Universitaires Pitie Salpetriere - Charles Foix
Paris, 75013
Gustave Roussy
Villejuif, 94805
Germany4 sites
Universitaetsklinikum Halle - Saale
Halle, 06120
Universitaetsklinikum Heidelberg
Heidelberg, 69120
Universitaetsklinikum Ulm
Ulm, 89081
Universitaetsklinikum Wuerzburg
Würzburg, 97078
South Korea4 sites
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 13620
Seoul National University Hospital
Seoul, 03080
Severance Hospital Yonsei University Health System
Seoul, 03722
Asan Medical Center
Seoul, 05505
Taiwan4 sites
National Cheng Kung University Hospital
Tainan, 70403
National Taiwan University Hospital
Taipei, 10002
Taipei Veterans General Hospital
Taipei, 11217
Linkou Chang Gung Memorial Hospital of Chang Gung Medical Foundation
Taoyuan, 33305
Australia3 sites
Chris OBrien Lifehouse
Camperdown, New South Wales, 2050
Epworth Healthcare
East Melbourne, Victoria, 3002
Peter MacCallum Cancer Centre
Parkville, Victoria, 3050
Japan3 sites
National Cancer Center Hospital
Chuo-ku, Tokyo, 104-0045
National Cancer Center Hospital East
Kashiwa-shi, Chiba, 277-8577
Aichi Cancer Center
Nagoya, Aichi-ken, 464-8681
Austria2 sites
Medizinische Universitaet Graz
Graz, 8036
Landeskrankenhaus Salzburg
Salzburg, 5020
Canada2 sites
Cross Cancer Institute
Edmonton, Alberta, T6G 1Z2
Princess Margaret Cancer Centre
Toronto, Ontario, M5G 2M9
Hong Kong2 sites
Queen Mary Hospital, The University of Hong Kong
Hong Kong
Prince of Wales Hospital, Chinese University of Hong Kong
Shatin, New Territories
United Kingdom2 sites
Sarah Cannon Research Institute UK
London, W1G 6AD
Royal Marsden Hospital
Sutton, SM2 5PT
About this study
Official title: A Phase 1/1b/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Anvumetostat Alone and in Combination With Docetaxel in Subjects With Advanced MTAP-null Solid Tumors
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
- Being tested
- Anvumetostat, Docetaxel, Comparator Anvumetostat Test Tablet
- 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
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Biliary Tract Neoplasms, Squamous Cell Carcinoma of Head and Neck, Esophageal Neoplasms, Stomach Neoplasms, Glioma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AnvumetostatDrug
Also called MTA Cooperative PRMT5 inhibitor, AMG 193
Anvumetostat: Orally via tablet
DocetaxelDrug
Docetaxel: Intravenous infusion
Comparator Anvumetostat Test TabletDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Anvumetostat; Drug: Docetaxel |
| Part 3: Anvumetostat Phase 2 | Experimental | Participants with MTAP-null solid tumors will receive Anvumetostat. Receives: 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. Receives: 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). Receives: 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. Receives: 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). Receives: Drug: Anvumetostat |
| Part 1i, Phase 1: Anvumetostat Dose Optimization | Experimental | Participants will receive a randomized dose optimization evaluation of Anvumetostat. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Anvumetostat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Parts 1 and 2: Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)
Measured: 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
Measured: Up to approximately 3 years
Part 3: Objective Response Rate (ORR)
Measured: Up to approximately 3 years
Secondary outcomes (26)
Parts 1 and 2: Maximal Plasma Concentration (Cmax) of Anvumetostat
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: 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
Measured: Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Cycle =21 days)
Parts 1 and 2: ORR
Measured: Up to approximately 3 years
Parts 1, 2 and 3: Disease Control Rate (DCR)
Measured: Up to approximately 3 years
Parts 1, 2 and 3: Duration of Response (DoR)
Measured: Up to approximately 3 years
Parts 1, 2 and 3: Time to Response (TTR)
Measured: Up to approximately 3 years
Parts 1, 2 and 3: Duration of Disease Control (DC)
Measured: Up to approximately 3 years
Parts 1, 2 and 3: Progression-Free Survival (PFS)
Measured: Up to approximately 3 years
Parts 1, 2 and 3: Overall Survival (OS)
Measured: Up to approximately 5 years
Part 3 Only: Number of Participants Who Experience TEAE
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 event
Measured: Up to approximately 3 years
Part 1a Only: Maximal Plasma Concentration (Cmax) of Anvumetostat
Measured: Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days)
Part 1a Only: Time to Achieve Maximal Plasma Concentration (Tmax) of Anvumetostat
Measured: Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days)
Part 1a Only: Area Under the Plasma Concentration Versus Time Curve (AUC) of Anvumetostat
Measured: Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days)
Part 1a Only: Maximal Plasma Concentration (Cmax) of Comparator Anvumetostat Test Tablet
Measured: 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 Anvumetostat Test Tablet
Measured: 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 Anvumetostat Test Tablet
Measured: Cycle 2 Day 2 to pre-dose on Cycle 2 Day 3 (Cycle = 28 days)
Part 1k Only: Cmax of Anvumetostat during fasted state
Measured: Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Part 1k Only: Tmax of Anvumetostat during fasted state
Measured: Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Part 1k Only: AUC of Anvumetostat during fasted state
Measured: Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Part 1k Only: Cmax of Anvumetostat during fed state
Measured: Cycle 2 day 2 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Part 1k Only: Tmax of Anvumetostat during fed state
Measured: Cycle 2 day 2 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Part 1k Only: AUC of Anvumetostat during fed state
Measured: Cycle 2 day 2 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2021
- Study start1 Feb 2022
- Primary completion30 Nov 2026 (estimated)
- Study completion30 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced MTAP-null Solid TumorsStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 329 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05094336
- Sponsor's protocol ID
- 20210023
- Other IDs
- 2023-504363-17, 2023
- Acronym
- MTAPESTRY 101
- Status last verified
- May 2026
- First submitted
- 14 Oct 2021
- Last updated
- 28 May 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1/1b/2 Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Anvumetostat Alone and in Combination With Docetaxel in Subjects With Advanced MTAP-null Solid Tumors
- ClinicalTrials.gov ID
- NCT05094336
- Acronym / sponsor ID
- MTAPESTRY 101 / 20210023
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 329 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 30 Nov 2026 (estimated)
- First posted
- 26 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 14
| Arm | Type | Receives |
|---|---|---|
| Part 1a, Phase 1: Anvumetostat Monotherapy Dose Exploration | Experimental | Drug: AnvumetostatParticipants with MTAP-null solid tumors will receive escalating doses of Anvumetostat to estimate the MTD and/or the RP2D. |
| Part 1c, Phase 1: Anvumetostat Monotherapy Dose Expansion | Experimental | Drug: AnvumetostatParticipants will receive the identified MTD/RP2D of Anvumetostat in the following cohort: MTAP-null NSCLC. |
| Part 2a, Phase 1: Anvumetostat Dose Exploration + Docetaxel | Experimental | Drug: Anvumetostat, Drug: DocetaxelParticipants with MTAP-null NSCLC will receive escalating doses of Anvumetostat + a fixed dose of docetaxel to estimate the MTD/RP2D of the combination. |
| Part 2b, Phase 1: Anvumetostat + Docetaxel Dose Expansion | Experimental | Drug: Anvumetostat, Drug: DocetaxelParticipants with MTAP-null NSCLC will receive the identified MTD/RP2D of Anvumetostat + docetaxel. |
| Part 3: Anvumetostat Phase 2 | Experimental | Drug: AnvumetostatParticipants with MTAP-null solid tumors will receive Anvumetostat. |
| Part 1e, Phase 1: Anvumetostat Monotherapy Dose Expansion | Experimental | Drug: AnvumetostatParticipants will receive the identified selected dose/MTD of Anvumetostat in the following cohort: MTAP-null BTC. |
| Part 1f, Phase 1: Anvumetostat Monotherapy Dose Expansion | Experimental | Drug: AnvumetostatParticipants will receive the identified selected dose/MTD of Anvumetostat in the following cohort: MTAP-null head and neck squamous cell carcinoma (HNSCC). |
| Part 1g, Phase 1: Anvumetostat Monotherapy Dose Expansion | Experimental | Drug: AnvumetostatParticipants will receive the identified selected dose/MTD of Anvumetostat in the following cohort: MTAP-null pancreatic adenocarcinoma. |
| Part 1h, Phase 1: Anvumetostat Monotherapy Dose Expansion | Experimental | Drug: AnvumetostatParticipants 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). |
| Part 1i, Phase 1: Anvumetostat Dose Optimization | Experimental | Drug: AnvumetostatParticipants will receive a randomized dose optimization evaluation of Anvumetostat. |
| Part 1j, Phase 1: Anvumetostat DSPS Substudy (US Sites Only) | Experimental | Drug: Anvumetostat, Drug: Comparator Anvumetostat Test TabletParticipants will receive doses of Anvumetostat and comparator Anvumetostat test tables at different times in a fasted state. |
| Part 1k, Phase 1: Anvumetostat Food Effect Substudy (US Sites Only) | Experimental | Drug: AnvumetostatParticipants will receive Anvumetostat once on a fasted state and once after eating a standardized high-fat, high calorie meal. |
| Part 1l, Phase 1: Anvumetostat Monotherapy Dose Expansion | Experimental | Drug: AnvumetostatParticipants will receive the identified selected dose/MTD of Anvumetostat in the following cohort: MTAP-null esophageal/gastric cancer. |
| Part 1m, Phase 1: Anvumetostat Monotherapy Dose Expansion | Experimental | Drug: AnvumetostatParticipants will receive the identified selected dose/MTD of Anvumetostat in the following cohort: MTAP-null glioma. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- 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.
Key exclusion criteria (26 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AnvumetostatAlso: MTA Cooperative PRMT5 inhibitor, AMG 193Anvumetostat: Orally via tablet | Drug | 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 |
| DocetaxelDocetaxel: Intravenous infusion | Drug | Part 2a, Phase 1: Anvumetostat Dose Exploration + Docetaxel, Part 2b, Phase 1: Anvumetostat + Docetaxel Dose Expansion |
| Comparator Anvumetostat Test TabletComparator 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. | Drug | Part 1j, Phase 1: Anvumetostat DSPS Substudy (US Sites Only) |
Primary outcome
Parts 1 and 2: Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)
Time frame: 28 days
Parts 1 and 2: Number of Participants Who Experience a Treatment-emergent Adverse Event (TEAE)
Time frame: Up to approximately 3 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 event
Part 3: Objective Response Rate (ORR)
Time frame: Up to approximately 3 years
26 secondary outcomes
Parts 1 and 2: Maximal Plasma Concentration (Cmax) of Anvumetostat
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Cycle =21 days)
Parts 1 and 2: ORR
Time frame: Up to approximately 3 years
Parts 1, 2 and 3: Disease Control Rate (DCR)
Time frame: Up to approximately 3 years
Parts 1, 2 and 3: Duration of Response (DoR)
Time frame: Up to approximately 3 years
Parts 1, 2 and 3: Time to Response (TTR)
Time frame: Up to approximately 3 years
Parts 1, 2 and 3: Duration of Disease Control (DC)
Time frame: Up to approximately 3 years
Parts 1, 2 and 3: Progression-Free Survival (PFS)
Time frame: Up to approximately 3 years
Parts 1, 2 and 3: Overall Survival (OS)
Time frame: Up to approximately 5 years
Part 3 Only: Number of Participants Who Experience TEAE
Time frame: Up to approximately 3 years
Part 1a Only: Maximal Plasma Concentration (Cmax) of Anvumetostat
Time frame: Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days)
Part 1a Only: Time to Achieve Maximal Plasma Concentration (Tmax) of Anvumetostat
Time frame: Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days)
Part 1a Only: Area Under the Plasma Concentration Versus Time Curve (AUC) of Anvumetostat
Time frame: Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days)
Part 1a Only: Maximal Plasma Concentration (Cmax) of Comparator Anvumetostat Test Tablet
Time frame: 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 Anvumetostat Test Tablet
Time frame: 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 Anvumetostat Test Tablet
Time frame: Cycle 2 Day 2 to pre-dose on Cycle 2 Day 3 (Cycle = 28 days)
Part 1k Only: Cmax of Anvumetostat during fasted state
Time frame: Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Part 1k Only: Tmax of Anvumetostat during fasted state
Time frame: Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Part 1k Only: AUC of Anvumetostat during fasted state
Time frame: Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Part 1k Only: Cmax of Anvumetostat during fed state
Time frame: Cycle 2 day 2 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Part 1k Only: Tmax of Anvumetostat during fed state
Time frame: Cycle 2 day 2 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Part 1k Only: AUC of Anvumetostat during fed state
Time frame: Cycle 2 day 2 pre-dose up to 24 hours post-dose (Cycle = 28 days)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2026.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
75 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Anvumetostat, Docetaxel and Comparator Anvumetostat Test Tablet in people with Advanced MTAP-null Solid Tumors, run by Amgen at 75 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 28 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 75 sites in United States, Belgium, China, Switzerland, France and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Parts 1 and 2: Number of Participants Who Experience a Dose-Limiting Toxicity (DLT) (time frame: 28 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2026.