Selection of patients for combination therapy
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Publication Number
US-11397184-B2
Publication Date
2022-07-26
Expiration Date
Abstract
Described herein are methods for selecting cancer patients for treatment with a combination therapy comprising entinostat and a second therapeutic agent. In particular, methods are provided for the examination of a non-cancer cell type, myeloid-derived suppressor cells, e.g., those which are CD14-positive and HLA-DR-(lo/negative), as a therapeutic indicator in the setting of entinostat combination therapies.
Core Innovation
The disclosed invention provides a method of selecting a patient for combination therapy comprising entinostat and a second therapeutic agent. The method is used in patients diagnosed with melanoma or lung cancer, and it is based on measurements made from a peripheral blood sample.
In the described method, the peripheral blood sample is obtained from the patient, and the number of myeloid derived suppressor cells and peripheral blood mononuclear cells is measured. The combination therapy is administered only if the ratio of myeloid derived suppressor cells to peripheral blood mononuclear cells falls within a specified range.
The specification relates the immunophenotyping measurements to entinostat’s immunomodulatory rationale, including supportive findings that show reduced MDSCs and increased HLA-DR+ monocytes in a clinical biomarker context. The biomarker approach is grounded in monitoring peripheral blood immune cell populations and using defined ratio criteria to select patients for entinostat-based combination therapy.
Claims Coverage
The relevant independent claim covers a patient-selection method for entinostat-based combination therapy in melanoma or lung cancer using ratio-based biomarker criteria derived from peripheral blood immune cell measurements. The inventive features are centered on selecting eligible patients based on the MDSC-to-PBMC ratio within a specified range.
Patient selection for entinostat combination therapy in melanoma or lung cancer
Obtaining a peripheral blood sample from the patient diagnosed with a melanoma or lung cancer, measuring the number of myeloid derived suppressor cells and peripheral blood mononuclear cells in the peripheral blood sample, and administering the combination therapy if the ratio of myeloid derived suppressor cells to peripheral blood mononuclear cells is between 1:200 and 1:4.
Subclass and marker specification for MDSCs
The method further specifies the myeloid-derived suppressor cell as a monocytic-MDSC and uses a cell surface marker that is CD14.
Expanded ratio constraints
The method defines that a stated ratio falls within one of several specified ranges, each bounded by 1:4 and a lower upper bound including 1:100, 1:50, 1:20, 1:10, or 1:5.
Restriction of the second therapeutic agent
The second therapeutic agent is either an anti-PD-1 antibody, an anti-PD-L1 antibody, or exemestane.
Narrowed melanoma indication
The method is for treating melanoma cancer that is metastatic melanoma.
Overall, the claims coverage centers on selecting patients for entinostat plus a second therapeutic agent using peripheral blood biomarker measurements, with eligibility determined by a defined MDSC-to-PBMC ratio range, and with dependent refinements that specify MDSC subtype/marker, expand ratio ranges, restrict the second therapeutic agent, and narrow the melanoma indication.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Not explicitly described in patent.
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