3310 LOGIC2: Phase 2, multi-center, open-label study of sequential encorafenib/binimetinib combination followed by a rational combination with targeted agents after progression, to overcome resistance in adult patients with locally-advanced or metastatic BRAF V600 melanoma

Dummer, Reinhard; Sandhu, Shahneen; Hassel, J.C.; Muñoz, Eva; Berking, Carola; Gesierich, Anja; Ascierto, P.A.; Esposito, O.; Carter, K.; Antona, V.; Radhakrishnan, R.; Cui, Xiaoyan; Caponigro, Giordano; Jaeger, Savina; Demuth, Tim; Miller, Wilson H.

doi:10.1016/s0959-8049(16)31828-7

Cited by 10 publications

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“…20 Promising clinical activity and tolerability of the combination of encorafenib and binimetinib were observed in patients with BRAFV600-mutated melanoma in a phase 1b/2 and a phase 2 study. 21,22 Further, the maximum tolerated dose of encorafenib, when combined with binimetinib, was higher than the maximum tolerated dose of encorafenib monotherapy, thus allowing the use of a higher encorafenib dose when combined with binimetinib in subsequent trials. 22 Here, we describe the results of the Part 1 of COLUMBUS trial, a phase 3 study of encorafenib plus binimetinib vs vemurafenib or encorafenib monotherapy in patients with advanced BRAFV600-mutant melanoma.…”

Section: Methods: Columbus (Combined Lgx818 Used With Mek162 In Braf-mentioning

confidence: 99%

Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF -mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial

Dummer¹,

Ascierto

Gogas

et al. 2018

The Lancet Oncology

771

671

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Section: Methods: Columbus (Combined Lgx818 Used With Mek162 In Braf-mentioning

confidence: 99%

Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF -mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial

Dummer¹,

Ascierto

Gogas

et al. 2018

The Lancet Oncology

771

671

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“…Patients with BRAF V600-or NRAS-mutated melanoma treated with BRAFi and/or MEKi (vemurafenib, dabrafenib, encorafenib, trametinib, binimetinib) within approved clinical trials (www.clinicaltrials.gov: NCT01543698, NCT02159066, NCT 01597908, NCT01909453, NCT01763164, NCT01436656, NCT01320085, NCT01820364, NCT01245062, NCT01682083) were included in this analysis. 9,12,[25][26][27][28][29][30][31][32] Written informed consent to use health-related data and biomaterial was obtained from all participants. Patients who withdrew consent and those whom unblinding was not possible were excluded.…”

Section: Methodsmentioning

confidence: 99%

The spectrum of cutaneous adverse events during encorafenib and binimetinib treatment in B‐rapidly accelerated fibrosarcoma‐mutated advanced melanoma

Graf

Koelblinger

Galliker

et al. 2018

Acad Dermatol Venereol

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Background B-rapidly accelerated fibrosarcoma (BRAF) inhibitor encorafenib alone and in combination with MEK inhibitor binimetinib improves survival in BRAF-mutated melanoma patients. So far, the range of cutaneous adverse events has been characterized only for established BRAF inhibitors (vemurafenib, dabrafenib) and MEK inhibitors (trametinib, cobimetinib).Objective The aim of this study was to investigate cutaneous adverse events emerging in melanoma patients treated with encorafenib and binimetinib.Methods Patients treated with BRAF and MEK inhibitors in clinical trials at the University Hospital of Zurich were identified. Frequency and features of cutaneous adverse events as well as their management were assessed based on the prospectively collected clinical and histopathological data. The events emerging during encorafenib and/or binimetinib therapy were compared to other BRAF and MEK inhibitors at the institution and in the literature. ResultsThe most frequent cutaneous adverse events observed in patients treated with encorafenib alone (n = 24) were palmoplantar hyperkeratosis (54%), palmoplantar erythrodysesthesia (58%) and alopecia (46%). Drug-induced papulopustular eruptions prevailed in patients with binimetinib monotherapy (n = 25). The most frequent cutaneous adverse events in patients treated with encorafenib/binimetinib (n = 49) were palmoplantar hyperkeratosis (10%).Conclusion Compared to data published for established BRAFi, encorafenib monotherapy showed less hyperproliferative cutaneous adverse events. In contrast, palmoplantar hyperkeratosis and palmoplantar erythrodysesthesia seem to occur more often. The combination of encorafenib and binimetinib is well tolerated and induces few cutaneous adverse events.

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“…109 A phase II trial evaluating encorafenib and binimetinib alone and in combination with a third agent after progression (LOGIC-2), reported an ORR of 68% for BRAF-and MEK-inhibitor na€ ıve patients, and 20% for non-na€ ıve patients, which is in accordance to results from other combinations. 110 Recent results from a phase III trial demonstrated a mPFS of 14.9 months vs. 7.3 months for vemurafenib monotherapy with a HR of 0.54 [95% CI 0.41e0.71, p < 0.001] vs. 9.6 months for encorafenib monotherapy with a HR of 0.75 [95% CI 0.56e1.00, p ¼ 0.051]. 111 In general, similar percentages of grade 3-4 adverse events were seen in both monotherapy and combination treatment.…”

Section: Studymentioning

confidence: 99%

Developments in targeted therapy in melanoma

Amann

Ramelyte

Thurneysen

et al. 2017

European Journal of Surgical Oncology (EJSO)

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Melanomas are disease entities driven in part by the mitogen activated protein kinase (MAPK) pathway. The TCGA network recently defined four genetic subtypes based on the most prevalent significantly mutated genes, including mutant BRAF, mutant RAS (N/H/K), mutant NF1, and Triple wild-type melanoma (harboring none of the aforementioned mutations, but instead includes KIT, GNA and GNAQ mutations). The successful development of kinase inhibitors marked a milestone in the treatment of metastatic melanoma. Combination treatment with a BRAF-and MEK-inhibitor is the current standard of care for inoperable stage IIIC/IV BRAF-mutated melanoma. Recent data demonstrate excellent longterm outcome, especially in patients with normal baseline LDH levels, and confirm that there is a subset of BRAF inhibitor-naive patients who experience durable responses without progression on combination treatment. In the future, adding a third compound based on individual genetic alterations might further improve the outcome of targeted therapy. AbstractMelanomas are disease entities driven in part by the mitogen activated protein kinase (MAPK) pathway. The TCGA network recently defined four genetic subtypes based on the most prevalent significantly mutated genes, including mutant BRAF, mutant RAS (N/H/K), mutant NF1, and Triple wild-type melanoma (harboring none of the aforementioned mutations, but instead includes KIT, GNA and GNAQ mutations).The successful development of kinase inhibitors marked a milestone in the treatment of metastatic melanoma. Combination treatment with a BRAF-and MEK-inhibitor is the current standard of care for inoperable stage IIIC/IV BRAF-mutated melanoma. Recent data demonstrate excellent long-term outcome, especially in patients with normal baseline LDH levels, and confirm that there is a subset of BRAF inhibitor-naive patients who experience durable responses without progression on combination treatment. In the future, adding a third compound based on individual genetic alterations might further improve the outcome of targeted therapy.

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3310 LOGIC2: Phase 2, multi-center, open-label study of sequential encorafenib/binimetinib combination followed by a rational combination with targeted agents after progression, to overcome resistance in adult patients with locally-advanced or metastatic BRAF V600 melanoma

Cited by 10 publications

References 0 publications

Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF -mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial

Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF -mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial

The spectrum of cutaneous adverse events during encorafenib and binimetinib treatment in B‐rapidly accelerated fibrosarcoma‐mutated advanced melanoma

Developments in targeted therapy in melanoma

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