Selection of patients for combination therapy
Inventors
Ordentlich, Peter • Wang, Lei • SANKOH, SERAP • Meyers, Michael
Assignees
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Publication Number
US-12000829-B2
Publication Date
2024-06-04
Expiration Date
Abstract
Described herein are methods for selecting cancer patients for treatment with a combination therapy comprising an HDAC inhibitor and a second therapeutic agent. In particular, methods are provided for the examination of a non-cancer cell type which are CD14-positive, HLA-DR-high and/or CD16-negative, as a therapeutic indicator in the setting of HDAC inhibitor combination therapies.
Core Innovation
The invention relates to selecting a patient for combination therapy comprising entinostat and an anti-PD-1 antibody. The patient is diagnosed with a cancer, and a peripheral blood sample is provided from the patient. The method determines whether to administer the combination therapy based on a measured peripheral-blood immune cell phenotype.
The method includes measuring the number of cells that are CD14-positive, HLA-DR-high, and CD16-negative in the peripheral blood sample. The number of total peripheral blood mononuclear cells is also measured. The decision to treat is made when the percentage of the CD14-positive, HLA-DR-high, and CD16-negative cells relative to total peripheral blood mononuclear cells is greater than a pre-determined percentage, wherein the pre-determined percentage is at least about 5%.
The disclosed cancer patient context includes selecting patients for treatment such as NSCLC or melanoma patients progressed on or unresponsive to prior PD-1/PD-L1 therapy. Entinostat is described in terms of immunomodulation, including reduction of MDSC, and the disclosure associates pairing an HDAC inhibitor such as entinostat with an immunotherapy agent.
Claims Coverage
The independent claim is clm-00001. It contains one primary selection-and-treatment inventive concept based on quantified peripheral-blood immune-cell markers relative to total peripheral blood mononuclear cells, together with a minimum pre-determined threshold of at least about 5%.
Selecting patients by CD14-positive, HLA-DR-high, CD16-negative fraction
providing a peripheral blood sample obtained from the patient, wherein the patient is diagnosed with a cancer; measuring the number of cells in the peripheral blood sample which are CD14-positive, HLA-DR-high, and CD16-negative; measuring the number of total peripheral blood mononuclear cells in the peripheral blood sample; administering the combination therapy if the percentage of the CD14-positive, HLA-DR-high, and CD16-negative cells relative to total peripheral blood mononuclear cells is greater than a pre-determined percentage
Minimum biomarker threshold for treatment
wherein the pre-determined percentage is at least about 5%
Overall, claim coverage is centered on a biomarker-driven patient selection criterion using CD14-positive, HLA-DR-high, and CD16-negative cells as a fraction of total peripheral blood mononuclear cells, with administration of entinostat plus an anti-PD-1 antibody when the fraction exceeds a pre-determined threshold.
Stated Advantages
Enables administering entinostat plus an anti-PD-1 antibody combination therapy to patients when the selected immune-cell fraction exceeds a pre-determined percentage threshold.
Documented Applications
Selecting cancer patients for combination therapy with entinostat and an anti-PD-1 antibody, including NSCLC and melanoma patients progressed on or unresponsive to prior PD-1/PD-L1 therapy.
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