Dabrafenib, Trametinib, and Spartalizumab for the Treatment of BRAF V600E or V600K Mutation Positive Stage IIIB/C/D Melanoma

PRIMARY OBJECTIVE: I. To determine the 12-month relapse free survival (RFS) rate in stage IIIB/C/D melanoma patients who, after 8 weeks of neoadjuvant dabrafenib and trametinib, do not achieve a pathologic complete response (pCR) and receive adjuvant dabrafenib, trametinib and spartalizumab. SECONDARY OBJECTIVES: I. To evaluate the safety of neoadjuvant dabrafenib and trametinib and adjuvant dabrafenib, trametinib and spartalizumab. II. To determine the 12-month relapse free survival (RFS) rate in stage IIIB/C/D. III. Melanoma patients who, after 8 weeks of neoadjuvant dabrafenib and trametinib, achieve a pCR and receive adjuvant dabrafenib and trametinib. IV. To assess the recurrence patterns, distant metastasis-free survival (DMFS), and overall survival (OS) in all patients treated on protocol. EXPLORATORY OBJECTIVES: I. To assess immunological and molecular features of treatment response and resistance. II. To assess circulating markers and correlate them with treatment response and relapse and toxicity III. To assess the impact of neoadjuvant therapy on surgical resectability. OUTLINE: NEOADJUVANT TREATMENT: Patients receive dabrafenib orally (PO) twice daily (BID) and trametinib PO once daily (QD) on days 1-28. Treatment repeats every 28 days for 2 cycles in the absence of disease progression or unacceptable toxicity. SURGERY: Patients undergo surgical resection of melanoma. ADJUVANT TREATMENT OF pCR PATIENTS: Patients receive dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeats every 28 days for 44 weeks in the absence of disease progression or unacceptable toxicity. ADJUVANT TREATMENT OF NON pCR PATIENTS: Patients receive spartalizumab intravenously (IV) over 30 minutes on day 1, dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeats every 28 days for 44 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3-4 months for 2 years.