Patent application EP19305173A (EP), filed 2019-02-11
Publication number: EP3693023A1
Title: USE OF ANTI-CEACAM5 IMMUNOCONJUGATES FOR TREATING LUNG CANCER
Abstract: [0001]    The present disclosure provides methods of treating high CEACAM5 expressing cancers including lung cancers such NSQ-NSCLC using immunoconjugates comprising an antibody that specifically binds human CEACAM5.
IPC codes: A61K  47/    68            A I
A61P  35/    00            A I
C07K  16/    30            A I
Claims: number: 1
text: An antibody for use in treating high carcinoembryonic antigen-related cell adhesion molecule 5 cancer in a subject in need thereof, wherein the antibody specifically binds human carcinoembryonic antigen-related cell adhesion molecule 5 (hCEACAM5) wherein the antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), wherein the VH comprises the three complementarity determining regions HCDR1, HCDR2 and HCDR3 and wherein the VL comprises the three CDRs LCDR1, LCDR2 and LCDR3, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 3 (GFVFSSYD); the HCDR2 comprises the amino acid sequence of SEQ ID NO: 4 (ISSGGGIT); the HCDR3 comprises the amino acid sequence of SEQ ID NO: 5 (AAHYFGSSGPFAY); the LCDR1 comprises the amino acid sequence of SEQ ID NO: 6 (ENIFSY); the LCDR2 comprises the amino acid sequence of NTR; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 7 (QHHYGTPFT).
number: 2
text: An antibody for use in treating non squamous non-small cell lung cancer (NSQ NSCLC) in a subject in need thereof, wherein the antibody specifically hCEACAM5 wherein the antibody comprises a VH and a VL, wherein the VH comprises the three complementarity determining regions HCDR1, HCDR2 and HCDR3) and wherein the VL comprises the three CDRs LCDR1, LCDR2 and LCDR3, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 3 (GFVFSSYD); the HCDR2 comprises the amino acid sequence of SEQ ID NO: 4 (ISSGGGIT); the HCDR3 comprises the amino acid sequence of SEQ ID NO: 5 (AAHYFGSSGPFAY); the LCDR1 comprises the amino acid sequence of SEQ ID NO: 6 (ENIFSY); the LCDR2 comprises the amino acid sequence of NTR; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 7 (QHHYGTPFT).
number: 3
text: An antibody for use in treating a subject that has been pre-treated with a cancer therapeutic , wherein the antibody specifically binds hCEACAM5 wherein the antibody comprises a VH and a VL, wherein the VH comprises the three complementarity determining regions HCDR1, HCDR2 and HCDR3) and wherein the VL comprises the three CDRs LCDR1, LCDR2 and LCDR3, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 3 (GFVFSSYD); the HCDR2 comprises the amino acid sequence of SEQ ID NO: 4 (ISSGGGIT); the HCDR3 comprises the amino acid sequence of SEQ ID NO: 5 (AAHYFGSSGPFAY); the LCDR1 comprises the amino acid sequence of SEQ ID NO: 6 (ENIFSY); the LCDR2 comprises the amino acid sequence of NTR; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 7 (QHHYGTPFT).
number: 4
text: The antibody for use according to claim 3, wherein the subject is a high carcinoembryonic antigen-related cell adhesion molecule expresser.
number: 5
text: The antibody for use according to any of claim 3, wherein the subject was pre-treated with an agent or drug for treatment of non-small cell lung cancer.
number: 6
text: The antibody for use according to claim 5, wherein the agent or drug is selected from the group consisting of: a chemotherapy agent, an angiogenesis inhibitor, an epidermal growth factor receptor (EGFR) inhibitor, an anaplastic lymphoma kinase (ALK) inhibitor, a receptor tyrosine kinase (ROS1) inhibitor, and an immune checkpoint inhibitor.
number: 7
text: The antibody for use according to claim 6, wherein the immune checkpoint inhibitor is a PD-1 inhibitor and/or a PD-L1 inhibitor.
number: 8
text: The antibody for use according to any of claims 1-3, wherein the VH comprises SEQ ID NO: 1
number: 13
text: The antibody for use according to claim 12, wherein said growth inhibitory agent is a cytotoxic agent.
number: 14
text: The antibody for use according to claim 12 or 13, wherein said growth inhibitory agent is selected from the group consisting of chemotherapeutic agents, enzymes, antibiotics, and toxins such as small molecule toxins or enzymatically active toxins, taxoids, vincas, taxanes, maytansinoid or maytansinoid analogs, tomaymycin or pyrrolobenzodiazepine derivatives, cryptophycin derivatives, leptomycin derivatives, auristatin or dolastatin analogs, prodrugs, topoisomerase II inhibitors, DNA alkylating agents, anti-tubulin agents, and CC-1065 or CC-1065 analogs.
number: 15
text: The antibody for use according to claim 13 or 14, wherein said growth inhibitory agent is (N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine) DM1 or N2'-deacetyl-N-2'(4-methyl-4-mercapto-1-oxopentyl)-maytansine (DM4).
number: 16
text: The antibody for use according to claim 15, wherein said growth inhibitory agent is DM4.
number: 17
text: The antibody for use according to any one of claims 12-16, wherein the antibody is covalently attached via a cleavable or non-cleavable linker to the at least one growth inhibitory agent.
number: 18
text: The antibody for use according to claim 17, wherein said linker is selected from the group consisting of N-succinimidyl pyridyldithiobutyrate (SPDB), 4-(Pyridin-2-yldisulfanyl)-2-sulfo-butyric acid (sulfo-SPDB), and succinimidyl (N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC).
number: 19
text: The antibody for use according to claim 18, wherein said linker is SPDB.
number: 20
text: The antibody for use according to any of claims 1-19, wherein the antibody is huMAb2-3.
number: 21
text: The antibody for use according to any of claims 1-20, wherein the subject has a hCEACAM5 expression of a percent score greater than or equal to 50 (consisting of 2+ and 3+ intensities) in the tumor cells populations, for example, the a percent score greater than or equal to about 50, about 50 to about 80, or 100 (consisting of 2+ and 3+ intensities).
number: 22
text: The antibody for use according to any of claims 1-21, wherein the antibody is administered by intravenously.
number: 23
text: The antibody for use according to claim 22, wherein the antibody is administered at a rate of 2.5 mg/min for the first 30 minutes or 1 hour.
number: 24
text: The antibody for use according to claim 23, wherein, after the 30 minutes, the rate is increased to 5 mg/min.
number: 25
text: The antibody for use according to claim 23 or 24, wherein the antibody is administered at a dose level of 5, 10, 20, 30, 40, 60, 80, 100, 120, 150, 180, or 210 mg/m<2> based on the body surface area of the subject.
number: 26
text: The antibody for use according to any of claims 1-25, wherein the antibody is administered at every 14 days, or every 3 weeks.
number: 27
text: The antibody for use according to any of claims 1-26, wherein, prior to administering the antibody, the subject is administered a pre-medication with histamine H1 antagonist.
number: 28
text: The antibody for use according to claim 27, wherein the histamine H1 antagonist is diphenylhydramine.
number: 29
text: The antibody for use according to claim 27, wherein the histamine H1 antagonist is dexchlorpheniramine.
number: 30
text: The antibody for use according to any of the preceding claims, wherein progression of at least one symptom of cancer is reduced, slowed, halted, or otherwise ameliorated.
number: 31
text: The antibody for use according to claim 30, wherein the tumor growth rate is reduced after treatment with the antibody.
number: 32
text: The antibody for use according to claim 30, wherein the tumor size is reduced after treatment with the antibody.
number: 33
text: The antibody for use according to claim 30, wherein the expression pattern, intensity and proportion of expressing cells indicates a reduction, slowing or halting of the cancer.
number: 34
text: A pharmaceutical composition comprising the antibody according to any one of claims 1-31, and a pharmaceutically acceptable carrier.
number: 35
text: A method for treating high carcinoembryonic antigen-related cell adhesion molecule 5 cancer in a subject in need thereof, the method comprising administering an antibody that specifically binds hCEACAM5 wherein the antibody comprises a VH and a VL, wherein the VH comprises the three complementarity determining regions HCDR1, HCDR2 and HCDR3) and wherein the VL comprises the three CDRs LCDR1, LCDR2 and LCDR3, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 3 (GFVFSSYD); the HCDR2 comprises the amino acid sequence of SEQ ID NO: 4 (ISSGGGIT); the HCDR3 comprises the amino acid sequence of SEQ ID NO: 5 (AAHYFGSSGPFAY); the LCDR1 comprises the amino acid sequence of SEQ ID NO: 6 (ENIFSY); the LCDR2 comprises the amino acid sequence of NTR; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 7 (QHHYGTPFT).
number: 36
text: A method for treating non squamous non-small cell lung cancer (NSQ NSCLC) in a subject in need thereof, the method comprising administering an antibody that specifically binds hCEACAM5 wherein the antibody comprises a VH and a VL, wherein the VH comprises the three complementarity determining regions HCDR1, HCDR2 and HCDR3) and wherein the VL comprises the three CDRs LCDR1, LCDR2 and LCDR3, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 3 (GFVFSSYD); the HCDR2 comprises the amino acid sequence of SEQ ID NO: 4 (ISSGGGIT); the HCDR3 comprises the amino acid sequence of SEQ ID NO: 5 (AAHYFGSSGPFAY); the LCDR1 comprises the amino acid sequence of SEQ ID NO: 6 (ENIFSY); the LCDR2 comprises the amino acid sequence of NTR; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 7 (QHHYGTPFT).
number: 37
text: A method for treating a subject that has been pre-treated with a cancer therapeutic, the method comprising administering an antibody that specifically binds hCEACAM5 wherein the antibody comprises a VH and a VL, wherein the VH comprises the three complementarity determining regions HCDR1, HCDR2 and HCDR3) and wherein the VL comprises the three CDRs LCDR1, LCDR2 and LCDR3, wherein the HCDR1 comprises the amino acid sequence of SEQ ID NO: 3 (GFVFSSYD); the HCDR2 comprises the amino acid sequence of SEQ ID NO: 4 (ISSGGGIT); the HCDR3 comprises the amino acid sequence of SEQ ID NO: 5 (AAHYFGSSGPFAY); the LCDR1 comprises the amino acid sequence of SEQ ID NO: 6 (ENIFSY); the LCDR2 comprises the amino acid sequence of NTR; and the LCDR3 comprises the amino acid sequence of SEQ ID NO: 7 (QHHYGTPFT).
number: 38
text: The method according to claim 37, wherein the subject is a high carcinoembryonic antigen-related cell adhesion molecule expresser.
number: 39
text: The method according to any of claim 37, wherein the subject was previously treated with an agent or drug for treatment of non-small cell lung cancer.
number: 40
text: The method according to claim 39, wherein the agent or drug is selected from the group consisting of: a chemotherapy agent, an angiogenesis inhibitor, an epidermal growth factor receptor (EGFR) inhibitor, an aplastic lymphoma kinase (ALK) inhibitor, a receptor tyrosine kinase (ROS1) inhibitor, and an immune checkpoint inhibitor.
number: 41
text: The method according to claim 40, wherein the immune checkpoint inhibitor is a PD-1 inhibitor and/or a PD-L1 inhibitor.
number: 42
text: The method according to any of claims 35-37, wherein the VH comprises SEQ ID NO: 1
number: 47
text: The method according to claim 46, wherein said growth inhibitory agent is a cytotoxic agent.
number: 48
text: The method according to claim 46 or 47, wherein said growth inhibitory agent is selected from the group consisting of chemotherapeutic agents, enzymes, antibiotics, and toxins such as small molecule toxins or enzymatically active toxins, taxoids, vincas, taxanes, maytansinoid or maytansinoid analogs, tomaymycin or pyrrolobenzodiazepine derivatives, cryptophycin derivatives, leptomycin derivatives, auristatin or dolastatin analogs, prodrugs, topoisomerase II inhibitors, DNA alkylating agenst, anti-tubulin agents, and CC-1065 or CC-1065 analogs.
number: 49
text: The method according to claim 47 or 48, wherein said growth inhibitory agent is (N2'-deacetyl-N2'-(3-mercapto-1-oxopropyl)-maytansine) DM1 orN2'-deacetyl-N-2'(4-methyl-4-mercapto-1-oxopentyl)-maytansine (DM4).
number: 50
text: The method according to claim 49, wherein said growth inhibitory agent is DM4.
number: 51
text: The method according to any one of claims 46-50, wherein the antibody is covalently attached via a cleavable or non-cleavable linker to the at least one growth inhibitory agent.
number: 52
text: The method according to claim 51, wherein said linker is selected from the group consisting of N-succinimidyl pyridyldithiobutyrate (SPDB), 4-(Pyridin-2-yldisulfanyl)-2-sulfobutyric acid (sulfo-SPDB), and succinimidyl (N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC).
number: 53
text: The method according to claim 51, wherein said linker is SPDB.
number: 54
text: The method according to any of claims 35-53, wherein the antibody is huMAb2-3.
number: 55
text: The method according to any of claims 35-54, wherein the subject has a a hCEACAM5 expression of a percent score greater than or equal to 50 (consisting of 2+ and 3+ intensities) in the tumor cells populations, for example, a percent score greater than or equal to about 50, about 50 to about 80, or 100 (consisting of 2+ and 3+ intensities).
number: 56
text: The method according to any of claims 35-55, wherein the antibody is administered by intravenously.
number: 57
text: The method according to claim 56, wherein the antibody is administered at a rate of 2.5 mg/min for the first 30 minutes or 1 hour.
number: 58
text: The method according to claim 57, wherein, after 30 minutes, the rate is increased to 5 mg/min.
number: 59
text: The method according to claim 57 or 58, wherein the antibody is administered at a dose level of 5, 10, 20, 30, 40, 60, 80, 100, 120, 150, 180, or 210 mg/m<2> based on the body surface area of the subject.
number: 60
text: The method according to any of claims 35-59, wherein the antibody is administered at every 14 days, or every 3 weeks.
number: 61
text: The method according to any of claims 35-60, wherein, prior to administering the antibody, the subject is administered a pre-medication with histamine H1 antagonist.
number: 62
text: The method according to claim 61, wherein the histamine H1 antagonist is diphenylhydramine or dexchlorpheniramine.
number: 63
text: The method of any of claims 35-62, wherein progression of at least one symptom of cancer is reduced, slowed, halted, or otherwise ameliorated.
number: 64
text: The method according to claim 63, wherein the tumor growth rate or tumor size is reduced after treatment with the antibody.
number: 65
text: The method according to claim 63, wherein the expression pattern, intensity and proportion of expressing cells indicates a reduction, slowing or halting of the cancer.
number: 66
text: The method of any of claims 35-65, wherein the antibody is administered as a pharmaceutical composition comprising a pharmaceutically acceptable carrier.
Office action: search_report, dated 2020-08-12
Rejection reasons: novelty_epc_54
inventive_step_epc_56
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Final disposition: pending (2020-08-12)