# US 2022/0033488 A1 · Cancer treatment by blocking host-induced il-1 in combination with radiotherapy

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- Number: US 2022/0033488 A1
- Document ID: US20220033488A1
- Status: Published application
- Kind: A1
- Application number: 17/451,332
- Filed: 2021-10-19
- Published: 2022-02-03
- Earliest claimed: 2018-05-29
- Assignees: OncoHost Ltd.
- Applicants: Oncohost Ltd.
- Inventors: Yuval SHAKED; Eyal JACOB; Ella FREMDER
- Web page: https://patentgrep.com/patent/US20220033488A1

## CPC

- C07K 16/245: {IL-1}
- C07K 16/2866: {against receptors for cytokines, lymphokines, interferons}
- A61K 38/005: {Enzyme inhibitors (protease inhibitors A61K38/55)}
- A61K 38/2006: {IL-1}
- A61K 39/001119: {Receptors for interleukins [IL]}
- A61N 5/10: X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy (A61N5/01 takes precedence)
- A61P 35/00: Antineoplastic agents
- G01N 33/53: Immunoassay; Biospecific binding assay; Materials therefor
- A61K 2039/505: {comprising antibodies}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- 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)
- A61N: ELECTROTHERAPY; MAGNETOTHERAPY; RADIATION THERAPY; ULTRASOUND THERAPY (measurement of bioelectric currents A61B; surgical instruments, devices or methods for transferring non-mechanical forms of energy to or from the body A61B18/00; anaesthetic apparatus in general A61M; incandescent lamps H01K; infrared radiators for heating H05B)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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)

## Abstract

Provided are blocking agents to IL-1α, IL-1β, or IL-1R activity for use in combination with radiotherapy for treating cancer patients in which radiotherapy treatment induces IL-1α, IL-1β or both in their circulation.

## Claims

### Claim 1

A method of treating a cancer patient, the method comprising:
a. measuring IL-1α, IL-1β or both in a biological sample obtained from said cancer patient at a time of 20 hours or more after a session of treatment with radiotherapy, to determine the level of circulating IL-1α, IL-1β or both in response to radiotherapy in said cancer patient, wherein said biological sample is selected from blood plasma, whole blood, blood serum or peripheral blood mononuclear cells;
b. obtaining a reference level for said circulating IL-1α, IL-1β or both in said cancer patient before said session of treatment with said radiotherapy;
c. establishing a fold-change in said circulating IL-1α, IL-1β or both from said reference level to said level in response to radiotherapy;
d. determining said cancer patient has a non-favorable response to said treatment with said radiotherapy if said fold-change is an increase of at least 1.5-fold; and
e. treating said cancer patient determined to have a non-favorable response with said radiotherapy in combination with a blocking agent selected from an IL-1R antagonist, an anti-IL-1β neutralizing monoclonal antibody or an anti-IL-1R neutralizing monoclonal antibody;
thereby treating a cancer patient.

### Claim 2 (depends on 1)

The method of claim 1, wherein said obtaining in step (b) is obtaining in a biological sample from said cancer patient before said session of treatment with said radiotherapy, wherein said biological sample is selected from blood plasma, whole blood, blood serum or peripheral blood mononuclear cells.

### Claim 3 (depends on 1)

The method of claim 1, wherein said biological sample of step (a) is blood plasma.

### Claim 4 (depends on 3)

The method of claim 3, wherein said obtaining in step (b) is obtaining in blood plasma from said cancer patient before said session of treatment with said radiotherapy.

### Claim 5 (depends on 1)

The method of claim 1, wherein said IL-1R antagonist is anakinra, and said treating is administering anakinra.

### Claim 6 (depends on 1)

The method of claim 1, wherein said blocking agent is anakinra and said treating is administering anakinra.

### Claim 7 (depends on 1)

The method of claim 1, wherein said anti-IL-1β neutralizing monoclonal antibody is selected from canakinumab, gevokizumab, LY2189102, and Lutikizumab (ABT-981), and said treating is administering at least one of canakinumab, gevokizumab, LY2189102, and Lutikizumab (ABT-981).

### Claim 8 (depends on 1)

The method of claim 1, wherein said anti-IL-1R neutralizing monoclonal antibody is selected from MEDI-8968 and GSK1827771, and said treating is administering at least one of MEDI-8968 or GSK1827771.

### Claim 9 (depends on 1)

The method of claim 1, wherein the blocking agent is selected from:
a. an IL-1R antagonist selected from anakinra, VRS-826, isunakinra and HL 2351;
b. an anti-IL-1β neutralizing monoclonal antibody selected from canakinumab, gevokizumab, LY2189102, and Lutikizumab (ABT-981); and
c. an anti-IL-1R neutralizing monoclonal antibody selected from MEDI-8968 and GSK1827771.

### Claim 10 (depends on 1)

The method of claim 1, wherein said treating comprises inhibiting tumor growth, increasing the number of CD8+T cytotoxic cells and decreasing the number of myeloid-derived suppressor cells (MDSCs), or a combination thereof.

### Claim 11 (depends on 1)

The method of claim 1, wherein said biological sample is obtained from the cancer patient at 20 to 24 hours after a session of treatment with standard radiotherapy schedule, or 20 to 72 hours after a session of treatment with accelerated/hypofractionated radiotherapy.

### Claim 12 (depends on 1)

The method of claim 1, wherein said session of treatment with radiotherapy is the first session of treatment with said radiotherapy.

### Claim 13 (depends on 1)

The method of claim 1, wherein said reference level is obtained in a reference biological sample obtained from said cancer patient at most 72 hours before said treatment with said radiotherapy.

### Claim 14 (depends on 13)

The method of claim 13, wherein said session of treatment with radiotherapy is not the first session of treatment with said radiotherapy, and wherein said reference level is obtained at least 72 hours after an earlier session of treatment with said radiotherapy, wherein said earlier session of treatment with said radiotherapy is a session of treatment before said not a first session of treatment with said radiotherapy.

### Claim 15 (depends on 1)

The method of claim 1, wherein said session of treatment with radiotherapy is not the first session of treatment with said radiotherapy, and wherein said reference level is obtained at least 72 hours after an earlier session of treatment with said radiotherapy, wherein said earlier session of treatment with said radiotherapy is a session of treatment before said not a first session of treatment with said radiotherapy.

### Claim 16 (depends on 1)

The method of claim 1, wherein the cancer patient suffers from a primary or a metastatic solid cancer selected from bladder cancer, breast cancer, brain cancer, cervical cancer, colon cancer, colorectal cancer, head and neck cancer, kidney cancer, lung cancer, melanoma, ovarian cancer, pancreatic cancer, prostate cancer, skin cancer, thyroid cancer, uterine cancer and sarcoma.

### Claim 17 (depends on 1)

The method of claim 1, wherein said treating comprises administering anakinra daily in a standard radiotherapy treatment schedule comprising 5 radiotherapy treatments a week for 5 to 9 weeks, or in an accelerated/hypofractionated radiotherapy treatment schedule comprising 2 radiotherapy treatments a week for 3 to 4 weeks and wherein the same total radiation dose is administered in both radiotherapy schedules.

### Claim 18 (depends on 1)

The method of claim 1, wherein anakinra is administered before, after or with each radiotherapy session.

### Claim 19 (depends on 17)

The method of claim 17, wherein said cancer is selected from breast cancer, colon cancer and brain cancer.

### Claim 20 (depends on 1)

The method of claim 1, wherein said anti-IL-1β neutralizing monoclonal antibody or an anti-IL-1α neutralizing monoclonal antibody is administered once every 2-3 weeks in a standard radiotherapy treatment schedule of 5 comprising 5 radiotherapy treatments a week for 5 to 9 weeks or in an accelerated/hypofractionated radiotherapy treatment schedule comprising 2 radiotherapy treatments a week for 3 to 4 weeks and wherein the same total radiation dose is administered in both radiotherapy schedules.