本研究旨在确定 MTA 协同 PRMT5 抑制剂 Anvumetostat 与其他治疗联合用于患有转移性或局部晚期甲基硫代腺苷磷酸化酶（MTAP）缺失胸腔肿瘤的成年受试者时的最大耐受剂量（MTD）或推荐联合剂量。
适应症：Thoracic Tumors、Non-small Cell Lung Cancer
入组条件
纳入标准
- Subprotocol A, B, and C
- Age ≥ 18 years (or ≥ legal age within the country if it is older than 18 years).
- Tumor tissue (formalin-fixed, paraffin-embedded sample) or an archival block must be available. Participants without archived tumor tissue available may be allowed to enroll by undergoing tumor biopsy before Anvumetostat dosing.
- Homozygous MTAP-deletion
- Able to swallow and retain PO administered study treatment.
- Disease measurable as defined by RECIST v1.1.
- Subprotocol A - Histologically or cytologically confirmed diagnosis of NSCLC.
- Arm A (Anvumetostat + carboplatin + paclitaxel + pembrolizumab):
- \- Predominantly squamous histology.
- Arm B (Anvumetostat + carboplatin + pemetrexed + pembrolizumab):
- \- Predominantly non-squamous histology.
- Arm C (Anvumetostat + pembrolizumab):
- \- PD-L1 positive.
- Subprotocol B - Histologically confirmed NSCLC with homozygous MTAP-deletion and KRAS p.G12C mutation.
- Subprotocol C
- Histologically or cytologically confirmed diagnosis of NSCLC with brain metastases.
- Brain lesion meeting RANO-BM criteria for measurable disease.
排除标准
- Subprotocol A, B, and C
- Gastrointestinal tract disease causing the inability to take PO medication, malabsorption syndrome, requirement for IV alimentation, gastric/jejunal tube feeds, uncontrolled inflammatory gastrointestinal disease (eg, Crohn's disease, ulcerative colitis).
- History of solid organ transplant.
- Major surgery within 28 days of first dose of Anvumetostat.
- Prior treatment with a MAT2A inhibitor or a PRMT5 inhibitor.
- Radiation therapy within 28 days of first dose.
- Subprotocol A
- \- Autoimmune disease or immunodeficiency disease as defined in the protocol'
入组条件维持 ClinicalTrials.gov 原始英文登记资料，实际入组资格以研究团队的正式评估与受试者知情同意书为准。资料来源：ClinicalTrials.gov，每两周自动更新，最后同步：2026年10月8日。