# US 2024/0197709 A1 · Potentiating the tumor-selective effects of nqo1-bioactivatable agent by use of cmet inhibitor

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- Number: US 2024/0197709 A1
- Document ID: US20240197709A1
- Status: Published application
- Kind: A1
- Application number: 18/541,121
- Filed: 2023-12-15
- Published: 2024-06-20
- Earliest claimed: 2022-12-20
- Applicants: The Trustees of Indiana University
- Inventors: Edward Ayson Motea; Snehal Bhandare
- Web page: https://patentgrep.com/patent/US20240197709A1

## CPC

- A61K 31/4545: containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
- A61K 31/352: condensed with carbocyclic rings, e.g. methantheline {(cannabinoids A61K31/658)}
- A61P 35/00: Antineoplastic agents
- 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

Methods are provided for treating cancer, particularly non-small cell lung cancers and pancreatic ductal adenocarcinomas, by administering both a sublethal dose of NAD(P)H:quinone oxidoreductase 1 (NQO1) bioactivatable drug and a sublethal dose of mesenchymal-epithelial transition factor (cMET) inhibitor to the cancer patient. Treatment of other cancers which overexpress cMET and NQO1 are also provided.

## Claims

### Claim 1

A method of treating cancer in a subject in need thereof comprising:
administering to the subject a NAD(P)H:quinone oxidoreductase 1 (NQO1) bioactivatable drug; and
administering to the subject a mesenchymal-epithelial transition factor (cMET) inhibitor.

### Claim 2 (depends on 1)

The method of claim 1, wherein the cancer cells of the subject exhibit increased mRNA expression of the NQO1 gene.

### Claim 3 (depends on 1)

The method of claim 1, wherein the cancer cells of the subject overexpress cMET.

### Claim 4 (depends on 1)

The method of claim 1, wherein the cancer cells of the subject overexpress both NQO1 and cMET.

### Claim 5 (depends on 1)

The method of claim 1, wherein the cancer cells of the subject are in the form of a solid tumor.

### Claim 6 (depends on 1)

The method of claim 1, wherein the subject has non-small cell lung cancer (NSCLC) or pancreatic ductal adenocarcinoma (PDA).

### Claim 7 (depends on 1)

The method of claim 1, wherein the NQO1 bioactivatable drug is selected from the group consisting of: β-lapachone (β-lap), β-lapachone (β-lap) analogue ARQ761, deoxynyboquinone (DNQ), DNQ derivative isobutyl-DNQ, napabucasin, streptonigrin, and Akt inhibitor KP372-1.

### Claim 8 (depends on 9)

The method of claim 9 wherein the NQO1 bioactivatable drug is β-lapachone (β-lap).

### Claim 9 (depends on 8)

The method of claim 8 wherein the dose of β-lapachone administered is less than 25 mg/kg.

### Claim 10 (depends on 1)

The method of claim 1, wherein the cMET inhibitor is selected from the group consisting of: crizotinib and cabozantinib.

### Claim 11 (depends on 10)

The method of claim 10 wherein the dose of crizotinib administered is less than 250 mg twice per day.

### Claim 12 (depends on 1)

The method of claim 1, wherein administering the cMET inhibitor occurs at least two hours prior to administering the NQO1 bioactivatable drug.

### Claim 13 (depends on 1)

The method of claim 1, administering the cMET inhibitor occurs simultaneously with administering the NQO1 bioactivatable drug.

### Claim 14 (depends on 1)

The method of claim 1, wherein the NQO1 bioactivatable drug is administered more than once.

### Claim 15 (depends on 1)

The method of claim 1, wherein the cMET inhibitor is administered more than once.

### Claim 16 (depends on 1)

The method of claim 1, wherein the NQO1 bioactivatable drug is administered at a sublethal dosage.

### Claim 17 (depends on 1)

The method of claim 1, wherein the cMET inhibitor is administered at a sublethal dosage.

### Claim 18 (depends on 1)

The method of claim 1, further comprising measuring a NQO1 activity and/or a cMET activity of the cancer cells in the subject, wherein the NQO1 activity and/or cMET activity are indicative of therapeutic effectiveness.

### Claim 19 (depends on 1)

The method of claim 1, further comprising administering to the subject a chemotherapeutic agent or an immunotherapeutic agent.

### Claim 20 (depends on 1)

The method of claim 1, wherein the subject is undergoing or subsequently undergoes radiotherapy.