AnvumetostatDocetaxelComparator Anvumetostat Test Tablet
Anvumetostat: Anvumetostat: Orally via tablet
Docetaxel: Docetaxel: Intravenous infusion
Comparator Anvumetostat Test Tablet: 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 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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
100 Years
Healthy volunteers
No
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 outcome measure(s)
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) — 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) — Up to approximately 3 years
Trial sites (75)
Facility
City
Region
Status
City of Hope National Medical Center
Duarte
California
California Research Institute
Glendale
California
Fomat Medical Research
Oxnard
California
University of California at SF
San Francisco
California
D and H Cancer Research Center
Margate
Florida
Boca Raton Clinical Research Medical Center Inc
Tamarac
Florida
Goshen Health Systems
Goshen
Indiana
Indiana University
Indianapolis
Indiana
Community Health Network MD Anderson Cancer Center - North
Indianapolis
Indiana
University of Maryland Medical Center
Baltimore
Maryland
American Oncology Partners, PA
Bethesda
Maryland
Henry Ford Cancer Detroit (Brigitte Harris Cancer Pavilion)
Detroit
Michigan
Washington University
St Louis
Missouri
Rutgers Cancer Institute of New Jersey
New Brunswick
New Jersey
Roswell Park Cancer Institute
Buffalo
New York
Northwell Health Monter Cancer Center
Lake Success
New York
New York University Grossman School of Medicine and New York University Langone Hospitals
New York
New York
Duke University
Durham
North Carolina
University Hospitals Cleveland Medical Center
Cleveland
Ohio
University of Pennsylvania
Philadelphia
Pennsylvania
Thomas Jefferson University
Philadelphia
Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh
Pennsylvania
Sanford Oncology Clinic and Pharmacy
Sioux Falls
South Dakota
Sarah Cannon Research Institute
Dallas
Texas
Center for Oncology and Blood Disorders
Houston
Texas
University of Texas MD Anderson Cancer Center
Houston
Texas
Lumi Research
Kingwood
Texas
South Texas Accelerated Research Therapeutics
San Antonio
Texas
University of Virginia Cancer Center
Charlottesville
Virginia
Virginia Cancer Specialists PC
Fairfax
Virginia
Chris OBrien Lifehouse
Camperdown
New South Wales
Epworth Healthcare
East Melbourne
Victoria
Peter MacCallum Cancer Centre
Parkville
Victoria
Medizinische Universitaet Graz
Graz
Austria
Landeskrankenhaus Salzburg
Salzburg
Austria
Universite Catholique de Louvain Cliniques Universitaires Saint Luc
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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