# US 2023/0263902 A1 · Anti-tissue factor antibody-drug conjugates and their use in the treatment of cancer > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2023/0263902 A1 - Document ID: US20230263902A1 - Status: Published application - Kind: A1 - Application number: 18/010,783 - Filed: 2021-06-29 - Published: 2023-08-24 - Earliest claimed: 2020-06-29 - Assignees: Genmab A/S - Applicants: Genmab A/S - Inventors: Reshma A. RANGWALA - Web page: https://patentgrep.com/patent/US20230263902A1 ## CPC - A61K 47/6889: {Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment} - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61K 47/68031: {the drug being an auristatin} - A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant} - A61P 35/00: Antineoplastic agents - C07K 16/36: against blood coagulation factors - A61K 9/0048: {Eye, e.g. artificial tears} - A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} - A61K 2039/505: {comprising antibodies} - A61K 2039/545: {characterised by the dose, timing or administration schedule} - C07K 2317/21: from primates, e.g. man - C07K 2317/70: characterized by effect upon binding to a cell or to an 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 The invention provides methods and compositions for treating cancer, such as advanced cervical cancer, in a subject, such as by the administration of antibody-drug conjugates that bind to tissue factor (TF). The invention also provides articles of manufacture and compositions comprising said antibody drug-conjugates that bind to TF for use in treating cancer (e.g., advanced cervical cancer). ## Claims ### Claim 1 A method of treating cervical cancer in a subject, the method comprising administering to the subject an antibody-drug conjugate that binds to tissue factor (TF), wherein the antibody-drug conjugate is tisotumab vedotin or a biosimilar thereof, and wherein the antibody-drug conjugate is administered at a dose of 2.0 mg/kg once every 3 weeks, wherein the subject has been previously treated with bevacizumab. ### Claim 2 (depends on 1) The method of claim 1, wherein the subject has an ECOG score of 0. ### Claim 3 (depends on 1) The method of claim 1, wherein the subject has an ECOG score of 1. ### Claim 4 (depends on 1, 2, 3) The method of any one of claims 1-3, wherein the subject is less than 65 years old. ### Claim 5 (depends on 1, 2, 3, 4) The method of any one of claims 1-4, wherein the subject has been previously treated with: a) paclitaxel and cisplatin, b) paclitaxel and carboplatin, or c) paclitaxel and topotecan. ### Claim 6 A method of treating cervical cancer in a subject, the method comprising administering to the subject an antibody-drug conjugate that binds to tissue factor (TF), wherein the antibody-drug conjugate is tisotumab vedotin or a biosimilar thereof, and wherein the antibody-drug conjugate is administered at a dose of 2.0 mg/kg once every 3 weeks, wherein the subject has not been previously treated with bevacizumab. ### Claim 7 (depends on 6) The method of claim 6, wherein the subject has an ECOG score of 0. ### Claim 8 (depends on 6) The method of claim 6, wherein the subject has an ECOG score of 1. ### Claim 9 (depends on 6, 7, 8) The method of any one of claims 6-8, wherein the subject is less than 65 years old. ### Claim 10 (depends on 6, 7, 8, 9) The method of any one of claims 6-9, wherein the subject has been previously treated with: a) paclitaxel and cisplatin, b) paclitaxel and carboplatin, or c) paclitaxel and topotecan. ### Claim 11 A method of treating cervical cancer in a subject, the method comprising administering to the subject an antibody-drug conjugate that binds to tissue factor (TF), wherein the antibody-drug conjugate is tisotumab vedotin or a biosimilar thereof, and wherein the antibody-drug conjugate is administered at a dose of 2.0 mg/kg once every 3 weeks, wherein the subject has an Eastern Cooperative Oncology Group (ECOG) score of 0. ### Claim 12 (depends on 11) The method of claim 11, wherein the subject is less than 65 years old. ### Claim 13 (depends on 11, 12) The method of any claim 11 or 12, wherein the subject has been previously treated with: a) paclitaxel and cisplatin, b) paclitaxel and carboplatin, or c) paclitaxel and topotecan. ### Claim 14 A method of treating cervical cancer in a subject, the method comprising administering to the subject an antibody-drug conjugate that binds to tissue factor (TF), wherein the antibody-drug conjugate is tisotumab vedotin or a biosimilar thereof, and wherein the antibody-drug conjugate is administered at a dose of 2.0 mg/kg once every 3 weeks, wherein the subject has an ECOG score of 1. ### Claim 15 (depends on 14) The method of claim 14, wherein the subject is less than 65 years old. ### Claim 16 (depends on 14, 15) The method of any claim 14 or 15, wherein the subject has been previously treated with: a) paclitaxel and cisplatin, b) paclitaxel and carboplatin, or c) paclitaxel and topotecan. ### Claim 17 A method of treating cervical cancer in a subject, the method comprising administering to the subject an antibody-drug conjugate that binds to tissue factor (TF), wherein the antibody-drug conjugate is tisotumab vedotin or a biosimilar thereof, and wherein the antibody-drug conjugate is administered at a dose of 2.0 mg/kg once every 3 weeks, wherein the subject is less than 65 years old. ### Claim 18 (depends on 17) The method of claim 17, wherein the subject has an ECOG score of 0. ### Claim 19 (depends on 17) The method of claim 17, wherein the subject has an ECOG score of 1. ### Claim 20 (depends on 17, 18, 19) The method of any one of claims 17-19, wherein the subject has been previously treated with: a) paclitaxel and cisplatin, b) paclitaxel and carboplatin, or c) paclitaxel and topotecan. ### Claim 21 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20) The method of any one of claims 1-20, wherein the objective response rate is between about 13% and about 35%, optionally, wherein the objective response rate is at least about 14%, about 19%, about 21%, 23.8%, about 24%, about 25%, about 26%, about 28%, about 30%, or about 33%. ### Claim 22 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21) The method of any one of claims 1-21, wherein the subject exhibits progression-free survival of at least about 3 months after administration of the antibody-drug conjugate, optionally, wherein the subject exhibits progression-free survival of at least about 4 months, about 5 months, or about 6 months after administration of the antibody-drug conjugate. ### Claim 23 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22) The method of any one of claims 1-22, wherein the subject exhibits overall survival of at least about 10 months after administration of the antibody-drug conjugate, optionally, wherein the subject exhibits overall survival of at least about 11 months, about 12 months, about 13 months, or 14 months after administration of the antibody-drug conjugate. ### Claim 24 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23) The method of any one of claims 1-23, wherein the duration of response to the antibody-drug conjugate is at least about 6 months after administration of the antibody-drug conjugate, optionally, wherein the duration of response to the antibody-drug conjugate is at least about 7 months, about 8 months or about 10 months after administration of the antibody-drug conjugate. ### Claim 25 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24) The method of any one of claims 1-24, wherein the time to response is less than about 6 months after administration of the antibody-drug conjugate, optionally, wherein the time to response is less than about 4 months, about 2 months, 1.4 months, or about 1.2 months after administration of the antibody-drug conjugate. ### Claim 26 A method of treating cervical cancer in a subject, the method comprising administering to the subject an antibody-drug conjugate that binds to tissue factor (TF), wherein the antibody-drug conjugate is tisotumab vedotin or a biosimilar thereof, and wherein the antibody-drug conjugate is administered at a dose of 2.0 mg/kg once every 3 weeks, wherein the objective response rate is between about 13% and about 35%, optionally, wherein the objective response rate is at least about 14%, about 19%, about 21%, 23.8%, about 24%, about 25%, about 26%, about 28%, about 30%, or about 33%. ### Claim 27 (depends on 26) The method of claim 26, wherein the subject exhibits progression-free survival of at least about 3 months after administration of the antibody-drug conjugate, optionally, wherein the subject exhibits progression-free survival of at least about 4 months, about 5 months, or about 6 months after administration of the antibody-drug conjugate. ### Claim 28 (depends on 26, 27) The method of claim 26 or 27, wherein the subject exhibits overall survival of at least about 10 months after administration of the antibody-drug conjugate, optionally, wherein the subject exhibits overall survival of at least about 11 months, about 12 months, about 13 months, or 14 months after administration of the antibody-drug conjugate. ### Claim 29 (depends on 26, 27, 28) The method of any one of claims 26-28, wherein the duration of response to the antibody-drug conjugate is at least about 6 months after administration of the antibody-drug conjugate, optionally, wherein the duration of response to the antibody-drug conjugate is at least about 7 months, about 8 months or about 10 months after administration of the antibody-drug conjugate. ### Claim 30 (depends on 26, 27, 28, 29) The method of any one of claims 26-29, wherein the time to response is less than about 6 months after administration of the antibody-drug conjugate, optionally, wherein the time to response is less than about 4 months, about 2 months, 1.4 months, or about 1.2 months after administration of the antibody-drug conjugate. ### Claim 31 A method of treating cervical cancer in a subject, the method comprising administering to the subject an antibody-drug conjugate that binds to tissue factor (TF), wherein the antibody-drug conjugate is tisotumab vedotin or a biosimilar thereof, and wherein the antibody-drug conjugate is administered at a dose of 2.0 mg/kg once every 3 weeks, wherein the subject exhibits progression-free survival of at least about 3 months after administration of the antibody-drug conjugate, optionally, wherein the subject exhibits progression-free survival of at least about 4 months, about 5 months, or about 6 months after administration of the antibody-drug conjugate. ### Claim 32 (depends on 31) The method of claim 31, wherein the objective response rate is between about 13% and about 35%, optionally, wherein the objective response rate is at least about 14%, about 19%, about 21%, 23.8%, about 24%, about 25%, about 26%, about 28%, about 30%, or about 33%. ### Claim 33 (depends on 31, 32) The method of claim 31 or 32, wherein the subject exhibits overall survival of at least about 10 months after administration of the antibody-drug conjugate, optionally, wherein the subject exhibits overall survival of at least about 11 months, about 12 months, about 13 months, or 14 months after administration of the antibody-drug conjugate. ### Claim 34 (depends on 31, 32, 33) The method of any one of claims 31-33, wherein the duration of response to the antibody-drug conjugate is at least about 6 months after administration of the antibody-drug conjugate, optionally, wherein the duration of response to the antibody-drug conjugate is at least about 7 months, about 8 months or about 10 months after administration of the antibody-drug conjugate. ### Claim 35 (depends on 31, 32, 33, 34) The method of any one of claims 31-34, wherein the time to response is less than about 6 months after administration of the antibody-drug conjugate, optionally, wherein the time to response is less than about 4 months, about 2 months, 1.4 months, or about 1.2 months after administration of the antibody-drug conjugate. ### Claim 36 A method of treating cervical cancer in a subject, the method comprising administering to the subject an antibody-drug conjugate that binds to tissue factor (TF), wherein the antibody-drug conjugate is tisotumab vedotin or a biosimilar thereof, and wherein the antibody-drug conjugate is administered at a dose of 2.0 mg/kg once every 3 weeks, wherein the subject exhibits overall survival of at least about 10 months after administration of the antibody-drug conjugate, optionally, wherein the subject exhibits overall survival of at least about 11 months, about 12 months, about 13 months, or 14 months after administration of the antibody-drug conjugate. ### Claim 37 (depends on 36) The method of claim 36, wherein the subject exhibits progression-free survival of at least about 3 months after administration of the antibody-drug conjugate, optionally, wherein the subject exhibits progression-free survival of at least about 4 months, about 5 months, or about 6 months after administration of the antibody-drug conjugate. ### Claim 38 (depends on 36, 37) The method of claim 36 or 37, wherein the objective response rate is between about 13% and about 35%, optionally, wherein the objective response rate is at least about 14%, about 19%, about 21%, 23.8%, about 24%, about 25%, about 26%, about 28%, about 30%, or about 33%. ### Claim 39 (depends on 36, 37, 38) The method of any one of claims 36-38, wherein the duration of response to the antibody-drug conjugate is at least about 6 months after administration of the antibody-drug conjugate, optionally, wherein the duration of response to the antibody-drug conjugate is at least about 7 months, about 8 months or about 10 months after administration of the antibody-drug conjugate. ### Claim 40 (depends on 36, 37, 38, 39) The method of any one of claims 36-39, wherein the time to response is less than about 6 months after administration of the antibody-drug conjugate, optionally, wherein the time to response is less than about 4 months, about 2 months, 1.4 months, or about 1.2 months after administration of the antibody-drug conjugate. ### Claim 41 A method of treating cervical cancer in a subject, the method comprising administering to the subject an antibody-drug conjugate that binds to tissue factor (TF), wherein the antibody-drug conjugate is tisotumab vedotin or a biosimilar thereof, and wherein the antibody-drug conjugate is administered at a dose of 2.0 mg/kg once every 3 weeks, wherein the duration of response to the antibody-drug conjugate is at least about 6 months after administration of the antibody-drug conjugate, optionally, wherein the duration of response to the antibody-drug conjugate is at least about 7 months, about 8 months or about 10 months after administration of the antibody-drug conjugate. ### Claim 42 (depends on 41) The method of claim 41, wherein the subject exhibits progression-free survival of at least about 3 months after administration of the antibody-drug conjugate, optionally, wherein the subject exhibits progression-free survival of at least about 4 months, about 5 months, or about 6 months after administration of the antibody-drug conjugate. ### Claim 43 (depends on 41, 42) The method of claim 41 or 42, wherein the subject exhibits overall survival of at least about 10 months after administration of the antibody-drug conjugate, optionally, wherein the subject exhibits overall survival of at least about 11 months, about 12 months, about 13 months, or 14 months after administration of the antibody-drug conjugate. ### Claim 44 (depends on 41, 42, 43) The method of any one of claims 41-43, wherein the objective response rate is between about 13% and about 35%, optionally, wherein the objective response rate is at least about 14%, about 19%, about 21%, 23.8%, about 24%, about 25%, about 26%, about 28%, about 30%, or about 33%. ### Claim 45 (depends on 41, 42, 43, 44) The method of any one of claims 41-44, wherein the time to response is less than about 6 months after administration of the antibody-drug conjugate, optionally, wherein the time to response is less than about 4 months, about 2 months, 1.4 months, or about 1.2 months after administration of the antibody-drug conjugate. ### Claim 46 A method of treating cervical cancer in a subject, the method comprising administering to the subject an antibody-drug conjugate that binds to tissue factor (TF), wherein the antibody-drug conjugate is tisotumab vedotin or a biosimilar thereof, and wherein the antibody-drug conjugate is administered at a dose of 2.0 mg/kg once every 3 weeks, wherein the time to response is less than about 6 months after administration of the antibody-drug conjugate, optionally, wherein the time to response is less than about 4 months, about 2 months, 1.4 months, or about 1.2 months after administration of the antibody-drug conjugate. ### Claim 47 (depends on 46) The method of claim 46, wherein the subject exhibits progression-free survival of at least about 3 months after administration of the antibody-drug conjugate, optionally, wherein the subject exhibits progression-free survival of at least about 4 months, about 5 months, or about 6 months after administration of the antibody-drug conjugate. ### Claim 48 (depends on 46, 47) The method of claim 46 or 47, wherein the subject exhibits overall survival of at least about 10 months after administration of the antibody-drug conjugate, optionally, wherein the subject exhibits overall survival of at least about 11 months, about 12 months, about 13 months, or 14 months after administration of the antibody-drug conjugate. ### Claim 49 (depends on 46, 47, 48) The method of any one of claims 46-48, wherein the duration of response to the antibody-drug conjugate is at least about 6 months after administration of the antibody-drug conjugate, optionally, wherein the duration of response to the antibody-drug conjugate is at least about 7 months, about 8 months or about 10 months after administration of the antibody-drug conjugate. ### Claim 50 (depends on 46, 47, 48, 49) The method of any one of claims 46-49, wherein the objective response rate is at least about between about 13% and about 35%, optionally, wherein the objective response rate is at least about 14%, about 19%, about 21%, 23.8%, about 24%, about 25%, about 26%, about 28%, about 30%, or about 33%. ### Claim 51 (depends on 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50) The method of any one of claims 26-50, wherein the subject has been previously treated with bevacizumab. ### Claim 52 (depends on 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50) The method of any one of claims 26-50, wherein the subject has not been previously treated with bevacizumab. ### Claim 53 (depends on 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52) The method of any one of claims 26-52, wherein the subject has experienced disease progression during or after treatment with: a) paclitaxel and cisplatin, b) paclitaxel and carboplatin, c) paclitaxel and topotecan, d) bevacizumab, paclitaxel, and cisplatin, e) bevacizumab, paclitaxel, and carboplatin, or f) bevacizumab, paclitaxel, and topotecan. ### Claim 54 (depends on 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53) The method of any one of claims 26-53, wherein the subject is less than 65 years old. ### Claim 55 (depends on 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54) The method of any one of claims 26-54, wherein the subject has an ECOG score of 0. ### Claim 56 (depends on 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54) The method of any one of claims 26-54, wherein the subject has an ECOG score of 1. ### Claim 57 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56) The method of any one of claims 1-56, wherein the cervical cancer is an adenocarcinoma. ### Claim 58 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56) The method of any one of claims 1-56, wherein the cervical cancer is an adenosquamous carcinoma. ### Claim 59 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56) The method of any one of claims 1-56, wherein the cervical cancer is a squamous cell carcinoma. ### Claim 60 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56) The method of any one of claims 1-56, wherein the cervical cancer is a non-squamous cell carcinoma. ### Claim 61 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60) The method of any one of claims 1-60, wherein the cervical cancer is recurrent or metastatic cervical cancer. ### Claim 62 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61) The method of any one of claims 1-61, wherein the subject has been previously treated with one or more therapeutic agents and did not respond to the treatment, wherein the one or more therapeutic agents is not the antibody-drug conjugate. ### Claim 63 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61) The method of any one of claims 1-61, wherein the subject has been previously treated with one or more therapeutic agents and relapsed after the treatment, wherein the one or more therapeutic agents is not the antibody-drug conjugate. ### Claim 64 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61) The method of any one of claims 1-61, wherein the subject has been previously treated with one or more therapeutic agents and has experienced disease progression during treatment, wherein the one or more therapeutic agents is not the antibody-drug conjugate. ### Claim 65 (depends on 62, 63, 64) The method of any one of claims 62-64, wherein the one or more therapeutic agents is a platinum-based therapeutic agent. ### Claim 66 (depends on 62, 63, 64) The method of any one of claims 62-64, wherein the one or more therapeutic agents is selected from the group consisting of: paclitaxel, cisplatin, carboplatin, topotecan, gemcitabine, fluorouracil, ixabepilone, imatinib mesylate, docetaxel, gefitinib, nab-paclitaxel, pemetrexed, vinorelbine, doxil, cetuximab, pembrolizumab, nivolumab and bevacizumab. ### Claim 67 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66) The method of any one of claims 1-66, wherein the subject is not a candidate for curative therapy. ### Claim 68 (depends on 67) The method of claim 67, wherein the curative therapy comprises radiotherapy and/or exenterative surgery. ### Claim 69 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66) The method of any one of claims 1-66, wherein the subject has received prior radiation to the pelvis. ### Claim 70 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66) The method of any one of claims 1-66, wherein the subject has not received prior radiation to the pelvis. ### Claim 71 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70) The method of any one of claims 1-70, wherein the subject has received one prior line of systemic therapy for relapsed, recurrent or metastatic cancer. ### Claim 72 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70) The method of any one of claims 1-70, wherein the subject has received two prior lines of systemic therapy for relapsed, recurrent or metastatic cancer. ### Claim 73 (depends on 71, 72) The method of any one of claims 71 or 72, wherein the subject did not respond to treatment with the prior systemic therapy. ### Claim 74 (depends on 71, 72) The method of any one of claims 71 or 72, wherein the subject relapsed after treatment with the prior systemic therapy. ### Claim 75 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74) The method of any one of claims 1-74, wherein the cervical cancer is an advanced stage cervical cancer, such as a stage 3 or stage 4 cervical cancer, such as metastatic cervical cancer. ### Claim 76 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75) The method of any one of claims 1-75, wherein the cervical cancer is recurrent cervical cancer. ### Claim 77 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76) The method of any one of claims 1-76, wherein the route of administration for the antibody-drug conjugate is intravenous. ### Claim 78 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77) The method of any one of claims 1-77, wherein at least about 0.1%, at least about 1%, at least about 2%, at least about 3%, at least about 4%, at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, or at least about 80% of the cervical cancer cells express TF. ### Claim 79 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78) The method of any one of claims 1-78, wherein the subject has a TF histology score (H-score) of at least 1. ### Claim 80 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79) The method of any one of claims 1-79, wherein the subject has one or more adverse events and is further administered an additional therapeutic agent to eliminate or reduce the severity of the one or more adverse events. ### Claim 81 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79) The method of any one of claims 1-79, wherein the subject is at risk of developing one or more adverse events and is further administered an additional therapeutic agent to prevent or reduce the severity of the one or more adverse events. ### Claim 82 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80) The method of any one of claims 1-80, wherein the subject has one or more adverse events and the dose of the antibody drug conjugate is reduced following the one or more adverse events. ### Claim 83 (depends on 82) The method of claim 82, wherein the dose is reduced from 2.0 mg/kg to 1.3 mg/kg. ### Claim 84 (depends on 83) The method of claim 83, wherein the dose is reduced from 1.3 mg/kg to 0.9 mg/kg. ### Claim 85 (depends on 80, 81, 82, 83, 84) The method of any one of claims 80-84, wherein the one or more adverse events is anemia, abdominal pain, hypokalemia, hyponatremia, epistaxis, fatigue, nausea, alopecia, conjunctivitis, constipation, decreased appetite, diarrhea, vomiting, peripheral neuropathy, or general physical health deterioration. ### Claim 86 (depends on 80, 81, 82, 83, 84, 85) The method of any one of claims 80-85, wherein the one or more adverse events is a grade 3 or greater adverse event. ### Claim 87 (depends on 80, 81, 82, 83, 84, 85) The method of any one of claims 80-85, wherein the one or more adverse events is a serious adverse event. ### Claim 88 (depends on 80, 81) The method of claim 80 or claim 81, wherein the one or more adverse events is conjunctivitis and/or keratitis and the additional agent is a preservative-free lubricating eye drop, an ocular vasoconstrictor and/or a steroid eye drop. ### Claim 89 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88) The method of any one of claims 1-88, wherein the antibody-drug conjugate is administered as a monotherapy. ### Claim 90 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89) The method of any one of claims 1-89, wherein the subject is a human. ### Claim 91 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90) The method of any one of claims 1-90, wherein the antibody-drug conjugate is in a pharmaceutical composition comprising the antibody-drug conjugate and a pharmaceutical acceptable carrier. ### Claim 92 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91) An antibody-drug conjugate that binds to TF for use in the method of any one of claims 1-91. ### Claim 93 (depends on 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91) Use of an antibody-drug conjugate that binds to TF for the manufacture of a medicament for use in the method of any one of claims 1-91.