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The FDA ( U.S. Food and Drug Administration ) has accepted and granted priority review for a new supplemental Biologics License Application ( sBLA ) for Keytruda ( Pembrolizumab ), an anti-PD-1 therapy.
The application seeks accelerated approval of Keytruda monotherapy for the treatment of adult and pediatric patients with unresectable or metastatic solid tumors with tissue tumor mutational burden-high ( TMB-H ) greater than or equal to 10 mutations/megabase, as determined by an FDA-approved test, who have progressed following prior treatment and who have no satisfactory alternative treatment options.

The application was based in part on results from the phase 2 KEYNOTE-158 trial, which also supported 2017 FDA approval for Keytruda as the first cancer treatment based on a biomarker, regardless of cancer type, in microsatellite instability-high ( MSI-H ) or mismatch repair deficient ( dMMR ) solid tumors.
MSI-H is on the highest end of the TMB spectrum.

KEYNOTE-158 is a multicenter, multi-cohort, non-randomized, open-label trial evaluating Pembrolizumab ( 200 mg every three weeks ) in patients with solid tumors.
Tissue TMB status was determined using the FoundationOne CDx assay.
Tumor response was assessed every nine weeks per RECIST ( Response Evaluation Criteria in Solid Tumors ) v1.1 by independent, central, blinded radiographic review.
The major efficacy outcome measures were objective response rate ( ORR ) and duration of response ( DOR ) as assessed by blinded independent central review ( BICR ) according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ.

Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells. ( Xagena )

Source: Merck, 2020

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