TY - JOUR
T1 - Longitudinal Genomic Analysis to Fine-tune Targeted Therapy
T2 - Results of the Phase II LOGIC 2 Trial in Patients with BRAFV600-Mutant Metastatic Melanoma
AU - Dummer, Reinhard
AU - Sandhu, Shahneen
AU - Miller, Wilson H.
AU - Butler, Marcus O.
AU - Taylor, Matthew H.
AU - Heinzerling, Lucie
AU - Blank, Christian U.
AU - Muñoz-Couselo, Eva
AU - Burris, Howard A.
AU - Postow, Michael A.
AU - Chmielowski, Bartosz
AU - Middleton, Mark R.
AU - Berking, Carola
AU - Hassel, Jessica C.
AU - Gesierich, Anja Heike
AU - Mauch, Cornelia
AU - Kleha, Joseph F.
AU - Polli, Anna
AU - Harney, Allison S.
AU - di Pietro, Alessandra
AU - Ascierto, Paolo A.
N1 - Publisher Copyright:
©2025 The Authors.
PY - 2025/6/1
Y1 - 2025/6/1
N2 - Purpose: LOGIC 2 (NCT02159066), a multicenter, open-label, two-part, phase II study, assessed encorafenib plus binimetinib combined with a third targeted agent after tumor progression on encorafenib plus binimetinib in patients with locally advanced, unresectable or metastatic BRAFV600-mutant melanoma. Patients and Methods: Adults with locally advanced, unresectable or metastatic BRAFV600-mutant melanoma who were BRAF inhibitor/MEK inhibitor (BRAFi/MEKi) treatment–naïve or pretreated received encorafenib plus binimetinib (part I/run-in). Based on the genomic testing at disease progression following encorafenib plus binimetinib, patients were assigned to one of four treatment arms to receive encorafenib plus binimetinib with an appropriate molecularly targeted agent (ribociclib, infigratinib, capmatinib, or buparlisib; part II). The primary endpoint was best overall response; safety, biomarkers, pharmacokinetics, and other efficacy endpoints were also assessed. Results: In part I/run-in, 75 BRAFi/MEKi-naïve patients and 83 BRAFi/MEKi-pretreated patients were treated; in part II, 58 patients were treated (ribociclib, n ¼ 38; infigratinib, n ¼ 1; capmatinib, n ¼ 13; buparlisib, n ¼ 6). The overall confirmed response rate was 73.3% [95% confidence interval (CI), 61.9–82.9] in BRAFi/MEKi-naïve patients, 25.3% (95% CI, 16.4–36.0) in pretreated patients, 2.6% (95% CI, 0.1–13.8) in the ribociclib arm, and 0% in the other three arms. Adverse events were manageable and consistent with the known safety profile of each drug. Conclusions: LOGIC 2 supports the use of encorafenib plus binimetinib for treatment-naïve and previously treated, locally advanced, unresectable or metastatic BRAFV600-mutant melanoma. However, adding a third targeted agent following disease progression did not show meaningful efficacy; further research is needed to identify other therapeutic targets to circumvent resistance.
AB - Purpose: LOGIC 2 (NCT02159066), a multicenter, open-label, two-part, phase II study, assessed encorafenib plus binimetinib combined with a third targeted agent after tumor progression on encorafenib plus binimetinib in patients with locally advanced, unresectable or metastatic BRAFV600-mutant melanoma. Patients and Methods: Adults with locally advanced, unresectable or metastatic BRAFV600-mutant melanoma who were BRAF inhibitor/MEK inhibitor (BRAFi/MEKi) treatment–naïve or pretreated received encorafenib plus binimetinib (part I/run-in). Based on the genomic testing at disease progression following encorafenib plus binimetinib, patients were assigned to one of four treatment arms to receive encorafenib plus binimetinib with an appropriate molecularly targeted agent (ribociclib, infigratinib, capmatinib, or buparlisib; part II). The primary endpoint was best overall response; safety, biomarkers, pharmacokinetics, and other efficacy endpoints were also assessed. Results: In part I/run-in, 75 BRAFi/MEKi-naïve patients and 83 BRAFi/MEKi-pretreated patients were treated; in part II, 58 patients were treated (ribociclib, n ¼ 38; infigratinib, n ¼ 1; capmatinib, n ¼ 13; buparlisib, n ¼ 6). The overall confirmed response rate was 73.3% [95% confidence interval (CI), 61.9–82.9] in BRAFi/MEKi-naïve patients, 25.3% (95% CI, 16.4–36.0) in pretreated patients, 2.6% (95% CI, 0.1–13.8) in the ribociclib arm, and 0% in the other three arms. Adverse events were manageable and consistent with the known safety profile of each drug. Conclusions: LOGIC 2 supports the use of encorafenib plus binimetinib for treatment-naïve and previously treated, locally advanced, unresectable or metastatic BRAFV600-mutant melanoma. However, adding a third targeted agent following disease progression did not show meaningful efficacy; further research is needed to identify other therapeutic targets to circumvent resistance.
UR - https://www.scopus.com/pages/publications/105007805029
U2 - 10.1158/1078-0432.CCR-24-0254
DO - 10.1158/1078-0432.CCR-24-0254
M3 - Article
C2 - 40106536
AN - SCOPUS:105007805029
SN - 1078-0432
VL - 31
SP - 2097
EP - 2107
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 11
ER -