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.

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

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.

Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.

Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.