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

Sponsor
University Hospital, Essen
Study ID
NCT02902029
Phase
PHASE2
Status
Completed

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

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

Study Details

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.

Key Dates

Start date
Nov 30, 2016
Status verified
Apr 2025
Primary completion
Mar 31, 2024
Completion
Mar 31, 2024

Study Design

Enrollment
186 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Arm A
    After a 3 months run-in period with vemurafenib and cobimetinib \[960 mg vemurafenib twice daily (BID), 28/0; 60 mg cobimetinib daily (QD), 21/7\], all patients who do not show disease progression or definite treatment interruption (e.g. due to unacceptable toxicity) for more than 28 days will be randomized. Further treatment with vemurafenib and cobimetinib (960 mg vemurafenib BID, 28/0; 60 mg cobimetinib QD, 21/7). After progression of disease patients in Arm A will subsequently receive atezolizumab treatment (1200 mg/ q3w).
  • Experimental: Arm B
    After a 3 months run-in period with vemurafenib and cobimetinib (960 mg vemurafenib BID, 28/0; 60 mg cobimetinib QD, 21/7), all patients who do not show disease progression or definite treatment interruption (e.g. due to unacceptable toxicity) for more than 28 days will be randomized. Further treatment with atezolizumab. Atezolizumab will be administered intravenously at a fixed dose of 1200 mg on day 1 of each 21 day-cycle. After progression of disease patients in Arm B will cross back to vemurafenib and cobimetinib treatment (960 mg vemurafenib BID, 28/0; 60 mg cobimetinib QD, 21/7).

Primary Outcome Measure

Time to First Documented Disease Progression [ Time Frame: 4 years ]

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