# US 2019/0167704 A1 · Therapeutic combinations comprising anti-folr1 immunoconjugates

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- Number: US 2019/0167704 A1
- Document ID: US20190167704A1
- Status: Published application
- Kind: A1
- Application number: 16/185,960
- Filed: 2018-11-09
- Published: 2019-06-06
- Earliest claimed: 2015-09-17
- Assignees: ImmunoGen, Inc.
- Applicants: ImmunoGen, Inc.
- Inventors: Jose PONTE; Jan PINKAS; Rodrigo R. RUIZ-SOTO
- Web page: https://patentgrep.com/patent/US20190167704A1

## CPC

- A61K 31/704: attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin {(digitoxin A61K31/7048)}
- A61K 31/555: containing heavy metals, e.g. hemin, hematin, melarsoprol
- A61K 33/24: Heavy metals; Compounds thereof
- A61K 33/243: Platinum; Compounds thereof
- A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines}
- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/68033: {the drug being a maytansine}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 47/6869: {the tumour determinant being from a cell of the reproductive system: ovaria, uterus, testes, prostate}
- A61P 35/00: Antineoplastic agents
- C07K 16/22: against growth factors {; against growth regulators}
- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- C07K 16/30: from tumour cells
- A61K 2039/505: {comprising antibodies}
- A61K 2039/507: {Comprising a combination of two or more separate antibodies}
- A61K 2039/545: {characterised by the dose, timing or administration schedule}
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- C07K 2317/565: Complementarity determining region [CDR]
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/75: Agonist effect on antigen
- 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
- 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)

## Abstract

Therapeutic combinations of immunoconjugates that bind to FOLR1 (e.g., IMGN853) with anti-VEGF agents (e.g., bevacizumab), a platinum-based agent, and/or doxorubicin are provided. Methods of administering the combinations to treat cancers, e.g., ovarian cancers, with greater clinical efficacy and/or decreased toxicity are also provided.

## Claims

### Claim at position 1

1-104. (canceled)

### Claim 105

A method for treating a patient having cancer comprising administering to said patient in need thereof:
(a) an immunoconjugate that binds to folate receptor 1 (FOLR1), wherein said immunoconjugate comprises
(i) an anti-FOLR1 antibody or antigen-binding fragment thereof comprising a heavy chain variable region (VH) complementary determining region (CDR)1 sequence of SEQ ID NO:9, a VH CDR2 sequence of SEQ ID NO:10, and a VH CDR3 sequence of SEQ ID NO:12, and a light chain variable region (VL) CDR1 sequence of SEQ ID NO:6, a VL CDR2 sequence of SEQ ID NO:7, and a VL CDR3 sequence of SEQ ID NO:8;
(ii) a sulfo-SPDB linker; and
(iii) a maytansinoid linked to the anti-FOLR1 antibody or antigen-binding fragment thereof by the sulfo-SPDB, and
(b) an anti-VEGF agent; and
(c) a platinum-based agent.

### Claim 106 (depends on 105)

The method of claim 105, wherein the anti-VEGF agent is bevacizumab.

### Claim 107 (depends on 105)

The method of claim 105, wherein the platinum-based agent is carboplatin.

### Claim 108 (depends on 105)

The method of claim 105, wherein the platinum-based agent is cisplatin.

### Claim 109 (depends on 105)

The method of claim 105, wherein the anti-VEGF agent is bevacizumab platinum-based agent is carboplatin.

### Claim 110 (depends on 109)

The method of claim 109, wherein the maytansinoid is DM4.

### Claim 111 (depends on 109)

The method of claim 109, wherein the anti-FOLR1 antibody or antigen-binding fragment thereof comprises a VH comprising the sequence of SEQ ID NO:3 and a VL comprising the sequence of SEQ ID NO:5.

### Claim 112 (depends on 109)

The method of claim 109, wherein the anti-FOLR1 antibody comprises (i) a heavy chain comprising the same amino acid sequence as the amino acid sequence of the heavy chain encoded by the plasmid deposited with the American Type Culture Collection (ATCC) as PTA-10772 and (ii) a light chain comprising the same amino acid sequence as the amino acid sequence of the light chain encoded by the plasmid deposited with the ATCC as PTA-10774, and wherein the maytansionid is DM4.

### Claim 113 (depends on 109)

The method of claim 109, wherein anti-FOLR1 antibody comprises (i) a heavy chain comprising the amino acid sequence of SEQ ID NO:13 and (ii) a light chain comprising the amino acid sequence of SEQ ID NO: 15, and wherein the maytansinoid is DM4.

### Claim 114 (depends on 109)

The method of claim 109, wherein the immunoconjugate is administered once every three weeks at a dose of 5 mg/kg adjusted ideal body weight (AIBW) or once every three weeks at a dose of 6 mg/kg AIBW.

### Claim 115 (depends on 109)

The method of claim 109, wherein the bevacizumab is administered once every three weeks at a dose of 15 mg/kg.

### Claim 116 (depends on 109)

The method of claim 109, wherein the carboplatin is administered once every three weeks at a dose to obtain an area under the curve (AUC) of 4 mg/ml·min, 5 mg/ml min, 6 mg/ml min, or 7 mg/ml min.

### Claim 117 (depends on 109)

The method of claim 109, which further comprises administration of a steroid to the patient, wherein the steroid is administered as an eye drop.

### Claim 118 (depends on 109)

The method of claim 109, which the immunoconjugate comprises from about 1 maytansinoid per antibody to about 8 maytansinoids per antibody.

### Claim 119 (depends on 109)

The method of claim 109, wherein the cancer is selected from the group consisting of ovarian cancer, cancer of the peritoneal, fallopian cancer, endometrial cancer, or lung cancer.

### Claim 120 (depends on 119)

The method of claim 119, wherein the ovarian cancer is platinum-resistant epithelial ovarian cancer.

### Claim 121 (depends on 119)

The method of claim 119, wherein the ovarian cancer is platinum sensitive recurrent epithelial ovarian cancer.

### Claim 122 (depends on 109)

The method of claim 109, wherein the cancer expresses FOLR1.

### Claim 123 (depends on 109)

The method of claim 109, wherein the FOLR1 expression is measured by immunohistochemistry (IHC).

### Claim 124 (depends on 123)

The method of claim 123, wherein at least 50% of cells or at least 75% of cells in a sample obtained from the patient have an IHC score of at least 2.

### Claim 125 (depends on 123)

The method of claim 123, wherein at least 50% of cells or at least 75% of cells in a sample obtained from the patient have an IHC score of at least 3.

### Claim 126 (depends on 109)

The method of claim 109, wherein the immunoconjugate, the bevacizumab and the carboplatin are administered in separate pharmaceutical compositions.

### Claim 127 (depends on 109)

The method of claim 109, wherein the cancer has previously been treated with bevacuzimab.

### Claim 128 (depends on 109)

The method of claim 109, wherein the cancer has not previously been treated with bevacuzimab.

### Claim 129 (depends on 109)

The method of claim 109, wherein the cancer is primary platinum refractory or platinum resistant.

### Claim 130 (depends on 109)

The method of claim 109, wherein the cancer is platinum sensitive.

### Claim 131 (depends on 109)

The method of claim 109, wherein the administration is a first-line therapy, a second-line therapy, a third-line, a fourth-line therapy, or a fifth-line therapy.