Compositions and methods for treating cancer with anti-egfr antibodies
AssigneeSymphogen A/S
InventorsMichael Kragh, Thomas Tuxen POULSEN, Cliff DING, Ivan David Horak
Life of this patent
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Abstract
The present invention provides methods and uses of anti-EGFR antibody compositions for treatment of cancers that are negative for certain mutations in RAS, BRAF, and the EGFR extracellular domain and are resistant to other anti-EGFR therapies.
Claims52
A method for treating cancer in a patient, comprising:
- a) selecting a patient with said cancer from whom a tumor DNA sample:
- i) has a mutant allele frequency (MAF) of less than 20% for (1) mutations in KRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- and (2) mutations in NRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- ii) has a MAF of less than 0.1% for BRAF mutation V600E;
- and
- iii) has a MAF of less than 0.1% for EGFR ECD mutations V441 D, V441G, S464L, G465E, G465R, and S492R, and
- b) administering to the patient an anti-EGFR antibody composition comprising two anti-human EGFR antibodies that bind to distinct epitopes in the EGFR extracellular domain (ECD).
A method for treating cancer in a patient, comprising:
- a) selecting a patient with said cancer from whom a tumor DNA sample:
- i) has a mutant allele frequency (MAF) of less than 20% for (1) mutations in KRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- and (2) mutations in NRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- and
- ii) has a MAF of less than 0.1% for BRAF mutation V600E, and
- b) administering to the patient an anti-EGFR antibody composition comprising two anti-human EGFR antibodies that bind to distinct epitopes in the EGFR extracellular domain (ECD).
A method for treating cancer in a human patient, comprising administering to the patient an anti-EGFR antibody composition comprising:
- a first anti-human EGFR antibody that comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 26 and a light chain comprising the amino acid sequence of SEQ ID NO:
- 24;
- and
- a second anti-human EGFR antibody that comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 27 and a light chain comprising the amino acid sequence of SEQ ID NO:
- 25;
- wherein the antibody composition is administered intravenously to the patient at a loading dose of 9 mg/kg, followed one week later by a weekly dose of 6 mg/kg.
A method for treating cancer in a human patient, comprising:
- a) selecting a patient with said cancer from whom a tumor DNA sample:
- i) has a mutant allele frequency (MAF) of less than 20% for (1) mutations in KRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- and (2) mutations in NRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146),
- ii) has a MAF of less than 0.1% for BRAF mutation V600E, and
- iii) has a MAF of less than 0.1% for EGFR ECD mutations V441D, V441G, S464L, G465E, G465R, and S492R;
- and
- b) administering to the patient an anti-EGFR antibody composition comprising:
- a first anti-human EGFR antibody that comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 26 and a light chain comprising the amino acid sequence of SEQ ID NO:
- 24;
- and
- a second anti-human EGFR antibody that comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 27 and a light chain comprising the amino acid sequence of SEQ ID NO:
- 25;
- wherein the antibody composition is administered intravenously to the patient at a loading dose of 9 mg/kg, followed one week later by a weekly dose of 6 mg/kg.
A method for treating cancer in a patient, comprising:
- a) selecting a patient with said cancer from whom a tumor DNA sample:
- i) has a mutant allele frequency (MAF) of less than 20% for (1) mutations in KRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- and (2) mutations in NRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146), and
- ii) has a MAF of less than 0.1% for of BRAF mutation V600E;
- and
- b) administering to the patient an anti-EGFR antibody composition comprising:
- a first anti-human EGFR antibody that comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 26 and a light chain comprising the amino acid sequence of SEQ ID NO:
- 24;
- and
- a second anti-human EGFR antibody that comprises a heavy chain comprising the amino acid sequence of SEQ ID NO:
- 27 and a light chain comprising the amino acid sequence of SEQ ID NO:
- 25;
- wherein the antibody composition is administered intravenously to the patient at a loading dose of 9 mg/kg, followed one week later by a weekly dose of 6 mg/kg.
Use of an antibody composition comprising two anti-human EGFR antibodies that bind to distinct epitopes in the EGFR extracellular domain (ECD) for the manufacture of a medicament for treating cancer in a patient, wherein a tumor DNA sample from the patient:
- i) has a mutant allele frequency (MAF) of less than 20% for (1) mutations in KRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- and (2) mutations in NRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- ii) has a MAF of less than 0.1% for BRAF mutation V600E;
- and
- iii) has a MAF of less than 0.1% for EGFR ECD mutations V441D, V441G, S464L, G465E, G465R, and S492R.
Use of an antibody composition comprising two anti-human EGFR antibodies that bind to distinct epitopes in the EGFR extracellular domain (ECD) for the manufacture of a medicament for treating cancer in a patient, wherein a tumor DNA sample from the patient:
- i) has a mutant allele frequency (MAF) of less than 20% for (1) mutations in KRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- and (2) mutations in NRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- and
- ii) has a MAF of less than 0.1% for BRAF mutation V600E.
An antibody composition comprising two anti-human EGFR antibodies that bind to distinct epitopes in the EGFR extracellular domain (ECD) for use in treating cancer in a patient in a method comprising:
- a) selecting a patient with said cancer from whom a tumor DNA sample:
- i) has a mutant allele frequency (MAF) of less than 20% for (1) mutations in KRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- and (2) mutations in NRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- ii) has a MAF of less than 0.1% for BRAF mutation V600E;
- and
- iii) has a MAF of less than 0.1% for EGFR ECD mutations V441 D, V441G, S464L, G465E, G465R, and S492R, and
- b) administering to the patient an anti-EGFR antibody composition comprising two anti-human EGFR antibodies that bind to distinct epitopes in the EGFR extracellular domain (ECD).
An antibody composition comprising two anti-human EGFR antibodies that bind to distinct epitopes in the EGFR extracellular domain (ECD) for use in treating cancer in a patient in a method comprising:
- a) selecting a patient with said cancer from whom a tumor DNA sample:
- i) has a mutant allele frequency (MAF) of less than 20% for (1) mutations in KRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- and (2) mutations in NRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- and
- ii) has a MAF of less than 0.1% for BRAF mutation V600E, and
- b) administering to the patient an anti-EGFR antibody composition comprising two anti-human EGFR antibodies that bind to distinct epitopes in the EGFR extracellular domain (ECD).
An article of manufacture suitable for treating cancer in a patient, comprising an antibody composition comprising two anti-human EGFR antibodies that bind to distinct epitopes in the EGFR extracellular domain (ECD), wherein said treatment comprises:
- a) selecting a patient with said cancer from whom a tumor DNA sample:
- i) has a mutant allele frequency (MAF) of less than 20% for (1) mutations in KRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- and (2) mutations in NRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- ii) has a MAF of less than 0.1% for BRAF mutation V600E;
- and
- iii) has a MAF of less than 0.1% for EGFR ECD mutations V441 D, V441G, S464L, G465E, G465R, and S492R, and
- b) administering to the patient the antibody composition.
An article of manufacture suitable for treating cancer in a patient, comprising an antibody composition comprising two anti-human EGFR antibodies that bind to distinct epitopes in the EGFR extracellular domain (ECD), wherein said treatment comprises:
- a) selecting a patient with said cancer from whom a tumor DNA sample:
- i) has a mutant allele frequency (MAF) of less than 20% for (1) mutations in KRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- and (2) mutations in NRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- and
- ii) has a MAF of less than 0.1% for BRAF mutation V600E, and
- b) administering to the patient the antibody composition.
A kit suitable for treating cancer in a patient from whom a tumor DNA sample:
- i) has a mutant allele frequency (MAF) of less than 20% for (1) mutations in KRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- and (2) mutations in NRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- ii) has a MAF of less than 0.1% for BRAF mutation V600E;
- and
- iii) has a MAF of less than 0.1% for EGFR ECD mutations V441D, V441G, S464L, G465E, G465R, and S492R,
- wherein the kit comprises an antibody composition comprising two anti-human EGFR antibodies that bind to distinct epitopes in the EGFR extracellular domain (ECD).
A kit suitable for treating cancer in a patient from whom a tumor DNA sample:
- i) has a mutant allele frequency (MAF) of less than 20% for (1) mutations in KRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- and (2) mutations in NRAS exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146);
- and
- ii) has a MAF of less than 0.1% for BRAF mutation V600E;
- wherein the kit comprises an antibody composition comprising two anti-human EGFR antibodies that bind to distinct epitopes in the EGFR extracellular domain (ECD).
Dependencies are inferred from the claim text.