NCT02902029

Evaluating the Efficacy and Safety of a Sequencing Schedule of Cobimetinib Plus Vemurafenib Followed by Immunotherapy With an Anti- PD-L1 Antibody in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma

A Phase II, Open-label, Randomized-controlled Trial Evaluating the Efficacy and Safety of a Sequencing Schedule of Cobimetinib Plus Vemurafenib Followed by Immunotherapy With an Anti- PD-L1 Antibody Atezolizumab for the Treatment in Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 186 (actual)
• Sponsor: University Hospital, Essen · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Most patients with locally advanced or metastatic tumors succumb to their disease. Thus, there is a substantial need for novel therapeutic strategies to improve the outcome for patients with advanced or metastatic melanoma. Targeting the the Ras/Raf signalling pathway by BRAF and MEK inhibition as well as targeting immunologic checkpoint control with an antiPD-L1 antibody have emerged as treatment option. In this study the best timing for sequential use of both treatment options (BRAF/MEK inhibition and antiPD-L1 antibody) in patients with unresectable or metastatic BRAFV600 mutant melanoma will be assessed.

Detailed description

At this time there is no experience concerning the sequencing strategy when using the two effective therapeutical approaches as targeting the Ras/Raf signalling pathway by BRAF and MEK inhibition or targeting immunologic checkpoint control with an antiPD-L1 antibody. This is a prospective, open, multicenter, randomized phase II study in patients with unresectable or metastatic BRAFV600 mutant melanoma. In this study the scheduling of the treatment with a combined BRAF/MEK inhibition and the treatment with an anti-PD-L1 antibody will be assessed. After a 3 months run-in period with vemurafenib and cobimetinib, all patients who did not show disease progression or treatment interruption for more than 28 days during run-in phase will be randomized in a 1:1 ratio: * either to proceed vemurafenib and cobimetinib until disease progression and subsequently cross-over to atezolizumab treatment until disease progression (Arm A). * or to receive the anti-PD-L1 antibody atezolizumab until disease progression and subsequently cross-back to vemurafenib and cobimetinib until disease progression (Arm B). In a translational research program tumor tissue, blood plasma and peripheral blood mononuclear cell will be analyzed to evaluate the biologic effects of treatment sequence on the molecular profile and biomarker expression in tissue and plasma.

Conditions

• Malignant Melanoma

Interventions

Type	Name	Description
DRUG	Vemurafenib	960 mg vemurafenib BID until progression or unacceptable toxicity develops
DRUG	Cobimetinib	60 mg cobimetinib QD, 21/7 until progression or unacceptable toxicity develops
DRUG	Atezolizumab	1200 mg atezolizumab administered intravenously on day 1 of each 21 day-cycle. Will be given until progression or unacceptable toxicity develops

Timeline

• Start date: 2016-11-01
• Primary completion: 2024-03-01
• Completion: 2024-03-01
• First posted: 2016-09-15
• Last updated: 2025-04-09

Locations

27 sites across 4 countries: France, Germany, Greece, Serbia