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

Brief summary public domain (ClinicalTrials.gov)

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.

Intervention public domain (ClinicalTrials.gov)

Drug: Anvumetostat. Anvumetostat: Orally via tablet

Intervention public domain (ClinicalTrials.gov)

Drug: Docetaxel. Docetaxel: Intravenous infusion

Intervention public domain (ClinicalTrials.gov)

Drug: 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.

Arm public domain (ClinicalTrials.gov)

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.

Arm public domain (ClinicalTrials.gov)

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.

Arm public domain (ClinicalTrials.gov)

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.

Arm public domain (ClinicalTrials.gov)

Part 2b, Phase 1: Anvumetostat + Docetaxel Dose Expansion (experimental): Participants with MTAP-null NSCLC will receive the identified MTD/RP2D of Anvumetostat + docetaxel.

Arm public domain (ClinicalTrials.gov)

Part 3: Anvumetostat Phase 2 (experimental): Participants with MTAP-null solid tumors will receive Anvumetostat.

Arm public domain (ClinicalTrials.gov)

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.

Primary outcome public domain (ClinicalTrials.gov)

Parts 1 and 2: Number of Participants Who Experience a Dose-Limiting Toxicity (DLT). Time frame: 28 days.

Primary outcome public domain (ClinicalTrials.gov)

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.

Primary outcome public domain (ClinicalTrials.gov)

Part 3: Objective Response Rate (ORR). Time frame: Up to approximately 3 years.

Secondary outcome public domain (ClinicalTrials.gov)

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).

Secondary outcome public domain (ClinicalTrials.gov)

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).

Secondary outcome public domain (ClinicalTrials.gov)

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).

Secondary outcome public domain (ClinicalTrials.gov)

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).

Secondary outcome public domain (ClinicalTrials.gov)

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).

Secondary outcome public domain (ClinicalTrials.gov)

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).

Eligibility public domain (ClinicalTrials.gov)

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 * …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 329 participants (actual).