SNPMiner Trials by Shray Alag


SNPMiner SNPMiner Trials (Home Page)


Report for Clinical Trial NCT02818023

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

Dose-seeking Study of Pembrolizumab Plus Vemurafenib and Cobimetinib for Therapy of Advanced Melanoma

The study plans to treat patients with pembrolizumab and thus blocking the PD-1/PD-L1 axis would render tumor-infiltrating lymphocytes (TILs) in the tumor parenchyma more functional as a consequence of BRAF inhibition, such that T cell activation by BRAFi would not be dampened by the PD-1/PD-L1 interaction. This combination would reverse dysfunction among T cells in the tumor parenchyma, maximizing T cell mediated immune anti-tumor efficacy. Progression free survival (PFS) with pembrolizumab in KEYNOTE-001 was 57% at 6 months, and 46.4% in the more recently reported phase III trial. PFS with vemurafenib treatment in BRIM-3 was ~50% at 6 months. Combined treatment with pembrolizumab, cobimetinib and vemurafenib for BRAF mutant melanoma is hypothesized to be safe and to improve the PFS compared to these recent historical controls. Because this combination has not yet been tested, and because the primary objective is to assess safety, the investigators are staging accrual in the first phase of the trial. The study aims to accrue up to 30 patients to the mTPI design of this study with the expectation that there will be at least 30 patients treated at RP2D. In case there are less than 30 patients on the RP2D, additional patients will be accrued. Patients will continue to receive treatment with pembrolizumab, vemurafenib and cobimetinib until disease progression or dose limiting toxicity. Patients with treatment response and no dose limiting toxicity may receive treatment with pembrolizumab for up to 24 months.

NCT02818023 Melanoma
MeSH:Melanoma
HPO:Cutaneous melanoma Melanoma

3 Interventions

Name: Pembrolizumab

Description: Pembrolizumab will be given at a dose of 200 mg q3 weeks (this is the standard dosage, ). Treatment with pembrolizumab and vemurafenib will commence on the same day. One cycle of treatment will be defined as one dose of pembrolizumab and 3 weeks of vemurafenib.
Type: Drug
Group Labels: 1

Pembrolizumab plus vemurafenib and Cobimetinib

Name: Vemurafenib

Description: Vemurafenib will be given at 480 mg twice daily, 720 mg twice daily, or 960 mg twice daily. Treatment with pembrolizumab and vemurafenib will commence on the same day. One cycle of treatment will be defined as one dose of pembrolizumab and 3 weeks of vemurafenib.
Type: Drug
Group Labels: 1

Pembrolizumab plus vemurafenib and Cobimetinib

Name: Cobimetinib

Description: Cobimetinib will be given at 20 mg once daily, 40 mg once daily, or 60 mg once daily. Treatment with cobimetinib will commence on the same day. Cobimetinib will be given daily for 21 days, then held for 7 days.
Type: Drug
Group Labels: 1

Pembrolizumab plus vemurafenib and Cobimetinib


Primary Outcomes

Description: determine the safety and maximum tolerated dose of vemurafenib and cobimetinib with pembrolizumab

Measure: Percentage of participants that experience a dose-limiting toxicity

Time: Up to 2 years

Secondary Outcomes

Measure: overall response rate (ORR)

Time: Up to 2 years

Measure: progression free survival

Time: Up to 2 years

Measure: overall survival

Time: up to 2 years

Other Outcomes

Measure: assessment of tumor microenvironment and immune response via biomarker level measurement

Time: Up to 2 years

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There are 2 SNPs

SNPs


1 V600E

Only patients with BRAF V600E or V600K mutated tumors will be enrolled. --- V600E ---


2 V600K

Only patients with BRAF V600E or V600K mutated tumors will be enrolled. --- V600E --- --- V600K ---



HPO Nodes


HPO: