# US 2021/0239697 A1 · Selection of patients for combination therapy

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- Number: US 2021/0239697 A1
- Document ID: US20210239697A1
- Status: Published application
- Kind: A1
- Application number: 17/053,559
- Filed: 2019-05-07
- Published: 2021-08-05
- Earliest claimed: 2018-05-07
- Assignees: Syndax Pharmaceuticals, Inc.
- Applicants: Syndax Pharmaceuticals, Inc.
- Inventors: Peter ORDENTLICH; Lei WANG; Serap SANKOH; Michael MEYERS
- Web page: https://patentgrep.com/patent/US20210239697A1

## CPC

- G01N 33/56966: {Animal cells}
- G01N 33/56977: {HLA or MHC typing}
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/0053: {Mouth and digestive tract, i.e. intraoral and peroral administration}
- A61K 31/4406: only substituted in position 3, e.g. zimeldine (nicotinic acid A61K31/455)
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61P 35/00: Antineoplastic agents
- G01N 33/56972: {White blood cells}
- G01N 33/5751: of the skin, e.g. melanoma
- G01N 33/5752: of the lungs
- A61K 2039/54: {characterised by the route of administration}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- G01N 2333/70535: Fc-receptors, e.g. CD16, CD32, CD64 (CD2314/705F)
- G01N 2333/70539: MHC-molecules, e.g. HLA-molecules
- G01N 2333/70596: Molecules with a "CD"-designation not provided for elsewhere in G01N2333/705
- G01N 2800/52: Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## 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.

## Claims

### Claim 1

A method of selecting a patient for combination therapy comprising an HDAC inhibitor and second therapeutic agent comprising:
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/or CD16-negative;
measuring the number of total peripheral blood mononuclear cells in the peripheral blood sample; and
administering the combination therapy if the percentage of the CD14-positive, HLA-DR-high, and/or CD16-negative cells relative to total peripheral blood mononuclear cells is greater than a pre-determined percentage.

### Claim 2

(canceled)

### Claim 3 (depends on 1)

The method of claim 1, wherein the patient progressed on a prior therapy with an anti-PD-1 antibody, an anti-PD-L1 antibody, a CTLA4-blocking antibody, or any combinations thereof.

### Claim 4 (depends on 3)

The method of claim 3, wherein the patient previously was considered unresponsive to the at least one prior therapy.

### Claim 5 (depends on 1)

The method of claim 1, comprising measuring the number of cells in the peripheral blood sample which are CD14-positive and HLA-DR-high, are CD14 positive and CD16-negative, or are HLA-DR-high and CD16-negative.

### Claim 6 (depends on 1)

The method of claim 1, comprising measuring the number of cells in the peripheral blood sample which are CD14-positive, HLA-DR-high and CD16-negative.

### Claim 7 (depends on 1)

The method of claim 1, wherein the peripheral blood sample is treated with an anticoagulant.

### Claim 8 (depends on 7)

The method of claim 7, wherein the anticoagulant is EDTA or heparin.

### Claim 9 (depends on 1)

The method of claim 1, wherein the pre-determined percentage is at least about 5%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45% or at least about 50%.

### Claim at position 10

10-18. (canceled)

### Claim 19 (depends on 1)

The method of claim 1, wherein the HDAC inhibitor is entinostat.

### Claim 20 (depends on 19)

The method of claim 19, wherein the entinostat is administered orally.

### Claim at position 13

21-22. (canceled)

### Claim 23 (depends on 19)

The method of claim 19, wherein the entinostat is administered every two weeks.

### Claim 24 (depends on 19)

The method of claim 19, wherein the entinostat is administered once every week during the treatment cycle, at a dose of 3 mg.

### Claim at position 16

25-27. (canceled)

### Claim 28 (depends on 1)

The method of claim 1, wherein the second therapeutic agent is an anti-PD-1 antibody.

### Claim 29 (depends on 28)

The method of claim 28, wherein the anti-PD-1 antibody is pembrolizumab.

### Claim at position 19

30-34. (canceled)

### Claim 35 (depends on 1)

The method of claim 1, wherein the cancer is a lung cancer.

### Claim 36 (depends on 35)

The method of claim 35, wherein the lung cancer is a non-small cell lung cancer, squamous cell carcinoma, or large cell carcinoma.

### Claim at position 22

37-42. (canceled)

### Claim 43 (depends on 1)

The method of claim 1, wherein entinostat and the second therapeutic agent are administered sequentially in either order or simultaneously.

### Claim 44 (depends on 1)

The method of claim 1, wherein the anti-PD-1 antibody is administered by infusion.

### Claim 45 (depends on 1)

The method of claim 1, wherein the patient has received at least one round of a prior therapy.

### Claim 46 (depends on 1)

The method of claim 1, wherein the patient has received at least three rounds of a prior therapy.

### Claim 47

A method of selecting a patient for combination therapy comprising entinostat and second therapeutic agent comprising:
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; and
administering the combination therapy if the percentage of the CD14-positive, HLA-DR-high and/or CD16-negative cells relative to total peripheral blood mononuclear cells is greater than a pre-determined percentage.

### Claim 48

(canceled)

### Claim 49

A method of selecting a patient for combination therapy comprising an entinostat and a second therapeutic agent comprising:
providing a peripheral blood sample from the patient, wherein the patient is diagnosed with non-small cell lung cancer and/or melanoma and progressed on and/or was considered unresponsive to prior PD-1 or PD-L1 therapy;
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; and
administering a combination therapy if the percentage of CD14-positive, HLA-DR-high, and CD16-negative cells relative to total live peripheral blood mononuclear cells is greater than a pre-determined percentage.

### Claim 50

(canceled)