Details

Autor(en) / Beteiligte

• Sullivan, Ryan J
• Hamid, Omid
• Gonzalez, Rene
• Infante, Jeffrey R
• Patel, Manish R
• Hodi, F Stephen
• Lewis, Karl D
• Tawbi, Hussein A
• Hernandez, Genevive
• Wongchenko, Matthew J
• Chang, YiMeng
• Roberts, Louise
• Ballinger, Marcus
• Yan, Yibing
• Cha, Edward
• Hwu, Patrick

Titel

Atezolizumab plus cobimetinib and vemurafenib in BRAF-mutated melanoma patients

Ist Teil von

• Nature medicine, 2019-06, Vol.25 (6), p.929-935

Ort / Verlag

United States

Erscheinungsjahr

2019

Quelle

MEDLINE

Beschreibungen/Notizen

• Melanoma treatment has progressed in the past decade with the development and approval of immune checkpoint inhibitors targeting programmed death 1 (PD-1) or its ligand (PD-L1) and cytotoxic T lymphocyte-associated antigen 4, as well as small molecule inhibitors of BRAF and/or MEK for the subgroup of patients with BRAF mutations . BRAF/MEK-targeted therapies have effects on the tumor microenvironment that support their combination with PD-1/PD-L1 inhibitors . This phase Ib study (ClinicalTrials.gov, number NCT01656642 ) evaluated the safety and anti-tumor activity of combining atezolizumab (anti-PD-L1) with vemurafenib (BRAF inhibitor), or cobimetinib (MEK inhibitor) + vemurafenib, in patients with BRAF -mutated metastatic melanoma. Triple combination therapy with atezolizumab + cobimetinib + vemurafenib, after a 28-d run-in period with cobimetinib + vemurafenib, had substantial but manageable toxicity. Exploratory biomarker data show that the cobimetinib + vemurafenib run-in was associated with an increase in proliferating CD4 T-helper cells but not with an increase in T-regulatory cells, as observed in the vemurafenib-only run-in period. The confirmed objective response rate was 71.8% (95% confidence interval 55.1-85.0). The estimated median duration of response was 17.4 months (95% confidence interval 10.6-25.3) with ongoing response in 39.3% of patients after 29.9 months of follow-up. Further investigation in a phase III trial is underway.