Σάββατο, 3 Δεκεμβρίου 2016

PEMBROLIZUMAB NEAR APPROVAL FOR MSI-H TUMORS

On November 28, the U.S. Food and Drug Administration (FDA) accepted for review the supplemental Biologics License Application (sBLA) for pembrolizumab (Keytruda) for the treatment of previously treated patients with advanced microsatellite instability–high (MSI-H) cancer. The FDA granted Priority Review with a target action date of March 8, 2017; the sBLA will be reviewed under the FDA’s Accelerated Approval program based on tumor response rate and durability of response. The FDA recently granted Breakthrough Therapy Designation to pembrolizumab for unresectable or metastatic MSI-H noncolorectal cancer, and previously granted it for the treatment of patients with unresectable or metastatic MSI-H colorectal cancer.
The application, which is seeking approval for pembrolizumab at a fixed dose of 200 mg every 3 weeks, is based on data from five uncontrolled, open-label, multi-cohort, multi-site phase I/II trials investigating the activity of pembrolizumab in MSI-H cancer.
Pembrolizumab is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. It blocks the interaction between programmed cell death protein 1 (PD-1) and its ligands, programmed cell death ligands 1 and 2 (PD-L1 and PD-L2), thereby activating T lymphocytes which may affect both tumor cells and healthy cells.
Microsatellites are short repetitive sequences of DNA found throughout the genome. Microsatellite instability—or MSI—is caused by a deficiency in the cell’s ability to repair errors in the DNA sequence (mismatch repair) that occur during cell division, leading to a characteristic change in microsatellite repeats. MSI-H is already an established biomarker in certain types of cancer. The presence of MSI is generally determined by an analytical test that compares the length of DNA from several microsatellite markers in tumor and normal cells, and produces a hallmark profile that distinguishes MSI-high, MSI-low, or microsatellite-stable tumor samples.
Pembrolizumab Indications and Dosing
Pembrolizumab indicated for the treatment of patients with unresectable or metastatic melanoma at a dose of 2 mg/kg every 3 weeks until disease progression or unacceptable toxicity.
In lung cancer, it indicated for the first-line treatment of patients with metastatic non–small cell lung cancer (NSCLC) whose tumors have high PD-L1 expression (tumor proportion score [TPS] ≥ 50%) as determined by an FDA-approved test, with no EGFR or ALK genomic tumor aberrations.
Pembrolizumab is also indicated for the treatment of patients with metastatic NSCLC whose tumors express PD-L1 (TPS ≥ 1%) as determined by an FDA-approved test, with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.
In metastatic NSCLC, pembrolizumab is administered at a fixed dose of 200 mg every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.
Pembrolizumab indicated for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma with disease progression on or after platinum-containing chemotherapy. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. In head and neck squamous cell carcinoma, pembrolizumab is administered at a fixed dose of 200 mg every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

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