本研究第1及第2部分的主要目標是評估Anvumetostat單獨使用及聯合docetaxel在患有轉移性或局部晚期甲基硫代腺苷磷酸化酶（MTAP）缺失實體瘤的成年參與者中的安全性、耐受性，並確定最大耐受劑量（MTD）或第二期推薦劑量（RP2D）。 本研究第3部分的主要目標是評估Anvumetostat在成年參與者中的療效。
適應症：Advanced MTAP-null Solid Tumors
收案條件
納入條件
- 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).
- Subject able and willing to eat a standardized high-fat, high-caloric meal
- Subject able and willing to fast for ≥ 6 hours
- \- Disease measurable as defined per Modified Response Assessment in Neuro-Oncology Criteria 2.0 (mRANO 2.0)
排除條件
- 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
收案條件維持 ClinicalTrials.gov 原始英文登錄資料，實際收案資格以研究團隊的正式評估與受試者同意書為準。資料來源：ClinicalTrials.gov，每兩週自動更新，最後同步：2026年10月8日。