TY - JOUR
TI - Randomized Phase III Trial Evaluating Spartalizumab Plus Dabrafenib and Trametinib for BRAF V600-Mutant Unresectable or Metastatic Melanoma.
AU - Dummer, Reinhard
AU - Long, Georgina V.
AU - Robert, Caroline
AU - Tawbi, Hussein A.
AU - Flaherty, Keith T.
AU - Ascierto, Paolo A.
AU - Nathan, Paul D.
AU - Rutkowski, Piotr
AU - Leonov, Oleg
AU - Dutriaux, Caroline
AU - Mandalà, Mario
AU - Lorigan, Paul
AU - Ferrucci, Pier Francesco
AU - Grob, Jean Jacques
AU - Meyer, Nicolas
AU - Gogas, Helen
AU - Stroyakovskiy, Daniil
AU - Arance, Ana
AU - Brase, Jan C.
AU - Green, Steven
AU - Haas, Tomas
AU - Masood, Aisha
AU - Gasal, Eduard
AU - Ribas, Antoni
AU - Schadendorf, Dirk
JO - Journal of clinical oncology: official journal of the American Society of Clinical Oncology
PY - 2022
VL - null
TODO - null
SP - JCO2101601
PB - 
SN - null
TODO - 10.1200/JCO.21.01601
TODO - null
TODO - PURPOSE: Preclinical data suggest the combination of an anti-programmed death receptor 1 antibody plus dabrafenib and trametinib to have superior antitumor  activity compared with dabrafenib plus trametinib alone. These observations are  supported by translational evidence suggesting that immune checkpoint inhibitors  plus targeted therapy may improve treatment outcomes in patients with BRAF  V600-mutant metastatic melanoma. COMBI-i is a phase III trial evaluating  spartalizumab, an anti-programmed death receptor 1 antibody, in combination with  dabrafenib and trametinib (sparta-DabTram), versus placebo plus dabrafenib and  trametinib (placebo-DabTram) in patients with BRAF V600-mutant unresectable or  metastatic melanoma. METHODS: Patients received spartalizumab 400 mg intravenously  every 4 weeks plus dabrafenib 150 mg orally twice daily and trametinib 2 mg orally  once daily or placebo-DabTram. Participants were age ≥ 18 years with unresectable or  metastatic BRAF V600-mutant melanoma. The primary end point was  investigator-assessed progression-free survival. Overall survival was a key  secondary end point (ClinicalTrials.gov identifier: NCT02967692). RESULTS: At data  cutoff (July 1, 2020), the median progression-free survival was 16.2 months (95\% CI,  12.7 to 23.9 months) in the sparta-DabTram arm versus 12.0 months (95\% CI, 10.2 to  15.4 months) in the placebo-DabTram arm (hazard ratio, 0.82 [95\% CI, 0.66 to 1.03];  P = .042 [one-sided; nonsignificant]). The objective response rates were 69\% (183 of  267 patients) versus 64\% (170 of 265 patients), respectively. Grade ≥ 3  treatment-related adverse events occurred in 55\% (146 of 267) of patients in the  sparta-DabTram arm and 33\% (88 of 264) in the placebo-DabTram arm. CONCLUSION: The  study did not meet its primary end point; broad first-line use of sparta-DabTram is  not supported by these results. Further biomarker-driven investigation may identify  patient subpopulations who could benefit from checkpoint inhibitor plus targeted  therapy combinations.
ER -