Ameloblastoma is the most common benign odontogenic tumor, characterized by high local invasiveness and a high recurrence rate. Currently, surgical treatment is the standard treatment modality. The main surgical approaches include radical resection represented by local extended resection (with a safety margin of more than 2 cm) and conservative procedures represented by curettage and fenestration. Although radical resection can effectively treat the disease, it often leads to severe jaw bone defects and even disrupts the continuity of the jaw bone. However, the conservative procedures have a recurrence rate of approximately 40%.

This study aims to reduce the recurrence rate of conservative procedures by using neoadjuvant therapy with dabrafenib combined with trametinib, and to reduce surgical trauma while improving the radical cure effect. The endpoints of this study are the 3-year and 5-year recurrence rates, as well as the effectiveness and safety of the neoadjuvant therapy.

The primary endpoints are the 3-year and 5-year recurrence - free survival rates after neoadjuvant therapy followed by curettage and fenestration surgery. The secondary endpoints are the radiological response, pathological response, and safety of the neoadjuvant therapy with dabrafenib combined with trametinib.

Inclusion Criteria:

• Age ≥ 12 years.
• Pathologically confirmed diagnosis of solid or cystic ameloblastic tumors, or recurrent unicystic ameloblastic tumors.
• Presence of BRAF V600E mutation confirmed by next-generation sequencing (NGS) in tumor tissue.
• Requires mandible resection at initial diagnosis (limited to segmental mandibulectomy, subtotal maxillectomy, or total maxillectomy).
• No distant metastasis or malignancy.
• ECOG performance status of 0-1.
• Willing to undergo surgical treatment after neoadjuvant therapy.
• No significant contraindications to MEK inhibitors or BRAF inhibitors.
• Adequate organ function as defined by the following standards: a) Hematologic criteria: WBC ≥ 4.0 × 10^9/L, ANC ≥ 1.5 × 10^9/L, PLT ≥ 100 × 10^9/L, Hb ≥ 90 g/L (no blood transfusion or blood products within the past 14 days, no G-CSF or other hematopoietic growth factors used to correct). b) Biochemical criteria: Serum albumin ≥ 3.0 g/dL (30 g/L), TBIL ≤ 1.5 × ULN, ALT, AST ≤ 2.5 × ULN, BUN and CRE ≤ 1.5 × ULN or estimated creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula). c) Normal coagulation function: Defined as INR or PT ≤ 1.5 × ULN; for patients on anticoagulant therapy, PT within the therapeutic range for the anticoagulant drug.
• Women of childbearing potential must have used reliable contraception, undergone a pregnancy test within 7 days prior to enrollment with a negative result, and be willing to continue using effective contraception during the study and for 16 weeks after the last dose of Trametinib combined with Dabrafenib. Male participants with female partners of childbearing potential should use effective contraception during the study and for 16 weeks after the last dose of Trametinib combined with Dabrafenib.

Exclusion Criteria:

• Previous treatment with Dabrafenib, Trametinib, or any other BRAF inhibitors or MEK inhibitors.
• Presence of active autoimmune disease. Subjects with stable autoimmune conditions not requiring systemic immunosuppressive therapy are allowed, such as: type 1 diabetes, hypothyroidism requiring only hormone replacement therapy, and skin conditions that do not require systemic treatment (e.g., vitiligo, psoriasis, alopecia).
• Congenital or acquired immunodeficiency (e.g., HIV infection), active hepatitis B (HBV-DNA ≥ 10^4 copies/ml), or hepatitis C (positive HCV antibodies with HCV RNA above the detection threshold of the testing method).
• Known allergy to the study drugs or any of their excipients; or a history of severe allergic reaction to other monoclonal antibodies or targeted therapies.
• History of myocardial infarction, severe/uncontrolled angina, NYHA class ≥2 heart failure, clinically significant supraventricular or ventricular arrhythmias, or symptomatic congestive heart failure within 6 months prior to enrollment.
• Receipt of a live vaccine within 4 weeks prior to first dose of study drug. Seasonal influenza vaccines are allowed if inactivated and injected, but live attenuated influenza vaccines (e.g., nasal spray) are not allowed.
• Known history of organ transplantation or hematopoietic stem cell transplantation.
• Known history of substance abuse or drug addiction.
• Pregnant or breastfeeding women.
• Diagnosis of any other malignancy within 5 years prior to study entry, except for cured localized skin basal cell carcinoma, squamous cell carcinoma, superficial bladder cancer, cervical carcinoma in situ, ductal carcinoma in situ of the breast, papillary thyroid carcinoma, and benign tumors.
• Presence of other serious physical or mental health conditions, or laboratory abnormalities that may increase the risk of participating in the study or interfere with the study results, as determined by the investigator.