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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
329
Anvumetostat: Orally via tablet
Docetaxel: Intravenous infusion
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.
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)
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
Time frame: Up to approximately 3 years
Part 3: Objective Response Rate (ORR)
Time frame: Up to approximately 3 years
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
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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
...and 65 more locations
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
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
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)