This phase II trial studies how well dabrafenib, trametinib, and spartalizumab works in treating patients with BRAF V600E or V600K mutation positive stage IIIB/C/D melanoma, who do not achieve a pathologic complete response after 8 weeks of dabrafenib and trametinib treatment. Patients who achieve a pathologic complete response after 8 weeks of neoadjuvant dabrafenib and trametinib will receive adjuvant dabrafenib and trametinib. Dabrafenib and trametinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as spartalizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving dabrafenib, trametinib, and spartalizumab may help to control melanoma.
Name: Dabrafenib
Name: Spartalizumab
Name: Therapeutic Conventional Surgery
Name: Trametinib
Description: Will be estimated with a 95% confidence interval by using the Kaplan-Meier method. Cox proportional hazards regression models will be fit to assess the association between various clinical, demographic, and disease covariates and RFS separately by pathologic response group.
Measure: Relapse-free survival (RFS) rate Time: From the time of surgery to any recurrence event, assessed up to 12 monthsDescription: The rate of grade 3+ adverse events will be tabulated and presented by group.
Measure: Incidence of adverse events Time: Up to 2 yearsDescription: Will be reported with 95% confidence intervals, and Cox regression models will be used to assess the association between similar covariates.
Measure: Overall survival Time: From treatment initiation to death, assessed up to 2 yearsDescription: Will be reported with 95% confidence intervals, and Cox regression models will be used to assess the association between similar covariates.
Measure: Distant metastasis-free survival Time: From treatment initiation to development of documented distant metastatic disease outside the loco-regional site of the primary tumor or lymph node metastasis, assessed up to 2 yearsDescription: Will be assessed quantitatively. Kruskal-Wallis tests will be used to compare these parameters at each time point between responders (pathological complete response [pCR]) and non-responders (no pCR). Changes in each parameter from baseline to surgery will also be compared between responders and non-responders.
Measure: Immune and molecular features of response and resistance Time: At baseline and at surgical resectionDescription: Markers and changes in markers over time will be compared between responders and non-responders by using Kruskal-Wallis tests. In addition, generalized linear mixed models may be used to model these markers over time.
Measure: Association between circulating blood markers and treatment response and relapse Time: At baseline, and assessed up to 2 yearsDescription: A survey will be provided to surgeons regarding the difficulty of surgery. These data will be subjective and will be summarized graphically as numbers permit.
Measure: Surgical resectability Time: Up to 2 yearsAllocation: N/A
Single Group Assignment
There are 2 SNPs
Dabrafenib, Trametinib, and Spartalizumab for the Treatment of BRAF V600E or V600K Mutation Positive Stage IIIB/C/D Melanoma This phase II trial studies how well dabrafenib, trametinib, and spartalizumab works in treating patients with BRAF V600E or V600K mutation positive stage IIIB/C/D melanoma, who do not achieve a pathologic complete response after 8 weeks of dabrafenib and trametinib treatment. --- V600E ---
Dabrafenib, Trametinib, and Spartalizumab for the Treatment of BRAF V600E or V600K Mutation Positive Stage IIIB/C/D Melanoma This phase II trial studies how well dabrafenib, trametinib, and spartalizumab works in treating patients with BRAF V600E or V600K mutation positive stage IIIB/C/D melanoma, who do not achieve a pathologic complete response after 8 weeks of dabrafenib and trametinib treatment. --- V600E --- --- V600K --- --- V600E ---
Only cases where a complete surgical resection with tumor- free margins can safely be achieved are defined as resectable - BRAF mutation-positive melanoma (V600E or V600K) based on report from a Clinical Laboratory Improvement Act (CLIA) certified laboratory - Patients must have measurable disease, defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 - Patients who have been previously treated in the adjuvant setting with ipilimumab or interferon alpha or investigational vaccines for melanoma will be eligible for treatment after a 28 day wash-out period - Patients who have previously received anti PD-1 in the adjuvant setting will be allowed if it has been six months or longer since previous drug exposure - Eastern Cooperative Oncology Group (ECOG) performance status 0-1 - Women of childbearing potential, defined as all women physiologically capable of becoming pregnant will be required to use highly effective methods of contraception during dosing and for 150-days after stopping treatment with spartalizumab. --- V600E ---
Dabrafenib, Trametinib, and Spartalizumab for the Treatment of BRAF V600E or V600K Mutation Positive Stage IIIB/C/D Melanoma This phase II trial studies how well dabrafenib, trametinib, and spartalizumab works in treating patients with BRAF V600E or V600K mutation positive stage IIIB/C/D melanoma, who do not achieve a pathologic complete response after 8 weeks of dabrafenib and trametinib treatment. --- V600E --- --- V600K ---
Dabrafenib, Trametinib, and Spartalizumab for the Treatment of BRAF V600E or V600K Mutation Positive Stage IIIB/C/D Melanoma This phase II trial studies how well dabrafenib, trametinib, and spartalizumab works in treating patients with BRAF V600E or V600K mutation positive stage IIIB/C/D melanoma, who do not achieve a pathologic complete response after 8 weeks of dabrafenib and trametinib treatment. --- V600E --- --- V600K --- --- V600E --- --- V600K ---
Only cases where a complete surgical resection with tumor- free margins can safely be achieved are defined as resectable - BRAF mutation-positive melanoma (V600E or V600K) based on report from a Clinical Laboratory Improvement Act (CLIA) certified laboratory - Patients must have measurable disease, defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 - Patients who have been previously treated in the adjuvant setting with ipilimumab or interferon alpha or investigational vaccines for melanoma will be eligible for treatment after a 28 day wash-out period - Patients who have previously received anti PD-1 in the adjuvant setting will be allowed if it has been six months or longer since previous drug exposure - Eastern Cooperative Oncology Group (ECOG) performance status 0-1 - Women of childbearing potential, defined as all women physiologically capable of becoming pregnant will be required to use highly effective methods of contraception during dosing and for 150-days after stopping treatment with spartalizumab. --- V600E --- --- V600K ---