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

NCT05094336
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Phase
Phase 1/Phase 2
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Recruitment status
Active, not recruiting
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Participants
329
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Lead sponsor
Amgen
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Start date
2022-02-01
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Number of sites
75
clinicaltrials.gov

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.
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Acronym
MTAPESTRY 101
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Short title
A Study of Anvumetostat in Participants With Advanced MTAP-null Solid Tumors (MTAPESTRY 101)
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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
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 1/Phase 2
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Study type
Interventional
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Completion date
2026-11-30
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First posted
2021-10-26
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Registry last updated
2026-05-28
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Primary completion date
2026-11-30
clinicaltrials.gov
Start date
2022-02-01
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Actual participants
329
clinicaltrials.gov
Participants
329
clinicaltrials.gov
Participant count basis
Actual
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Protocol amendments
9
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Number of sites
75
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Registry sponsor category
Industry
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Lead sponsor
Amgen
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05094336
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ClinicalTrials.gov ID
NCT05094336
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

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

    Timeframe: 28 days

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

    Timeframe: 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

  3. Part 3: Objective Response Rate (ORR)

    Timeframe: Up to approximately 3 years

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

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

  2. Parts 1 and 2: Time to Achieve Maximal Plasma Concentration (Tmax) of Anvumetostat

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

  3. Parts 1 and 2: Area Under the Plasma Concentration Versus Time Curve (AUC) of Anvumetostat

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

  4. Part 2 Only: Maximal Plasma Concentration (Cmax) of Docetaxel

    Timeframe: Cycle 1 Day 1 to Pre-Dose Cycle 5 Day 1 (Cycle =21 days)

  5. 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)

  6. 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)

  7. Parts 1 and 2: ORR

    Timeframe: Up to approximately 3 years

  8. Parts 1, 2 and 3: Disease Control Rate (DCR)

    Timeframe: Up to approximately 3 years

  9. Parts 1, 2 and 3: Duration of Response (DoR)

    Timeframe: Up to approximately 3 years

  10. Parts 1, 2 and 3: Time to Response (TTR)

    Timeframe: Up to approximately 3 years

  11. Parts 1, 2 and 3: Duration of Disease Control (DC)

    Timeframe: Up to approximately 3 years

  12. Parts 1, 2 and 3: Progression-Free Survival (PFS)

    Timeframe: Up to approximately 3 years

  13. Parts 1, 2 and 3: Overall Survival (OS)

    Timeframe: Up to approximately 5 years

  14. Part 3 Only: Number of Participants Who Experience TEAE

    Timeframe: Up to approximately 3 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 event

  15. Part 1a Only: Maximal Plasma Concentration (Cmax) of Anvumetostat

    Timeframe: Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days)

  16. Part 1a Only: Time to Achieve Maximal Plasma Concentration (Tmax) of Anvumetostat

    Timeframe: Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days)

  17. Part 1a Only: Area Under the Plasma Concentration Versus Time Curve (AUC) of Anvumetostat

    Timeframe: Cycle 2 Day 1 to pre-dose on Cycle 2 Day 2 (Cycle = 28 days)

  18. Part 1a Only: Maximal Plasma Concentration (Cmax) of Comparator Anvumetostat Test Tablet

    Timeframe: Cycle 2 Day 2 to pre-dose on Cycle 2 Day 3 (Cycle = 28 days)

  19. Part 1a Only: Time to Achieve Maximal Plasma Concentration (Tmax) of Comparator Anvumetostat Test Tablet

    Timeframe: Cycle 2 Day 2 to pre-dose on Cycle 2 Day 3 (Cycle = 28 days)

  20. Part 1a Only: Area Under the Plasma Concentration Versus Time Curve (AUC) of Comparator Anvumetostat Test Tablet

    Timeframe: Cycle 2 Day 2 to pre-dose on Cycle 2 Day 3 (Cycle = 28 days)

  21. Part 1k Only: Cmax of Anvumetostat during fasted state

    Timeframe: Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days)

  22. Part 1k Only: Tmax of Anvumetostat during fasted state

    Timeframe: Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days)

  23. Part 1k Only: AUC of Anvumetostat during fasted state

    Timeframe: Cycle 2 day 1 pre-dose up to 24 hours post-dose (Cycle = 28 days)

  24. Part 1k Only: Cmax of Anvumetostat during fed state

    Timeframe: Cycle 2 day 2 pre-dose up to 24 hours post-dose (Cycle = 28 days)

  25. Part 1k Only: Tmax of Anvumetostat during fed state

    Timeframe: Cycle 2 day 2 pre-dose up to 24 hours post-dose (Cycle = 28 days)

And 1 more, listed on the interactive page.

Sources for outcomes
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Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Maximum age
100 Years
Healthy volunteers
No

  • 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
Sources for eligibility
clinicaltrials.gov

  • City of Hope National Medical CenterDuarte, United States
  • California Research InstituteGlendale, United States
  • Fomat Medical ResearchOxnard, United States
  • University of California at SFSan Francisco, United States
  • D and H Cancer Research CenterMargate, United States
  • Boca Raton Clinical Research Medical Center IncTamarac, United States
  • Goshen Health SystemsGoshen, United States
  • Indiana UniversityIndianapolis, United States
  • Community Health Network MD Anderson Cancer Center - NorthIndianapolis, United States
  • University of Maryland Medical CenterBaltimore, United States
  • American Oncology Partners, PABethesda, United States
  • Henry Ford Cancer Detroit (Brigitte Harris Cancer Pavilion)Detroit, United States
  • Washington UniversitySt Louis, United States
  • Rutgers Cancer Institute of New JerseyNew Brunswick, United States
  • Roswell Park Cancer InstituteBuffalo, United States
  • Northwell Health Monter Cancer CenterLake Success, United States
  • New York University Grossman School of Medicine and New York University Langone HospitalsNew York, United States
  • Duke UniversityDurham, United States
  • University Hospitals Cleveland Medical CenterCleveland, United States
  • University of PennsylvaniaPhiladelphia, United States
  • Thomas Jefferson UniversityPhiladelphia, United States
  • University of Pittsburgh Medical CenterPittsburgh, United States
  • Sanford Oncology Clinic and PharmacySioux Falls, United States
  • Sarah Cannon Research InstituteDallas, United States
  • Center for Oncology and Blood DisordersHouston, United States

And 50 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2023
  • 2023-504363-17
Sources for references
clinicaltrials.gov

Related records

Drugs (2)

Lead sponsors (1)

Conditions (6)

Targets (15)