Anti-cancer combination comprising Anti-c-met antibody

Abstract

The present invention relates to: a combination comprising an antibody, or an antigen-binding fragment thereof, that specifically binds to a hepatocyte growth factor receptor (c-Met), and a second anticancer agent; and a use of the combination for the prevention and treatment of cancer. The combination therapy of the anti-c-Met antibody and the second anticancer agent of the present invention has excellent anticancer activity and exhibits a synergistic effect that can kill cancer cells even in cancers that are difficult to overcome due to drug resistance, and thus can be very usefully employed for the prevention and treatment of cancer.

Description

Description of the invention

Title of invention

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Background Art

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[0011] In any one of the above [1] to [1], the antibody may bind to an epitope region described by the amino acid sequence of SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315 and SEQ ID NO: 316.

[0012] In any one of the above [1] to

[0011] , the antibody or antigen-binding fragment thereof has a binding affinity for human c-Met of 1 x 10' 7 Binds with a KD of less than or equal to M, wherein the KD can be determined by surface plasmon resonance (Biacore) analysis.

[0013] In any one of the above [1] to

[0012] , the antibody may be an antibody comprising a light chain variable region comprising a light chain CDR1 as set forth in SEQ ID NO: 1; a light chain CDR2 as set forth in SEQ ID NO: 2; a light chain CDR3 as set forth in SEQ ID NO: 3; and a heavy chain variable region comprising a heavy chain CDR1 as set forth in SEQ ID NO: 4; a heavy chain CDR2 as set forth in SEQ ID NO: 5; and a heavy chain CDR3 as set forth in SEQ ID NO: 6, or an affinity-optimized antibody thereof.

[0014] In any one of the above [1] to

[0013] , the antibody may include a light chain variable region described in SEQ ID NO: 7 and a heavy chain variable region described in SEQ ID NO: 8.

[0015] In any one of the above [1] to

[0014] , the antibody may comprise (a) a light chain variable region described in SEQ ID NO: 11 and a heavy chain variable region described in SEQ ID NO: 13; or (b) a light chain variable region described in SEQ ID NO: 12 and a heavy chain variable region described in SEQ ID NO: 14.

[0016] In any one of the above [1] to

[0015] , the antibody may comprise a hinge region described in any one of SEQ ID NO: 19 to SEQ ID NO: 26.

[0017] In any one of the above [1] to

[0016] , the antibody comprises a light chain variable region comprising a light chain CDR1 as described in SEQ ID NO: 1; a light chain CDR2 as described in SEQ ID NO: 2; a light chain CDR3 as described in SEQ ID NO: 3, and a heavy chain variable region comprising a heavy chain CDR1 as described in SEQ ID NO: 4; a heavy chain CDR2 as described in SEQ ID NO: 5; and a heavy chain CDR3 as described in SEQ ID NO: 6, wherein at least one amino acid sequence is substituted in the antibody, wherein (i) G at the 1st position of the light chain CDR1 is A, E, K, L, N, R, S, V or W; A at the 2nd position is C, G, I, P, S, T or V; S at the 3rd position is G, M, N, P, Q, R, S or T; E at the 4th position is A, D, F, G, H, K, M, Q, R, S, T or V; N at the 5th position is A, D, E, G, K, L, P, Q, R, S, T or V; I in the 6th position is A, F, L, M, Q, R, S, T or V; Y in the 7th position is F, H, R or V; or G in the 8th position is D, F, H, M, N, R, S, T or V is substituted; (ii) G at position 1 of light chain CDR2 is D, F, H, K, P, Q, S, V or Y; T at the 3rd position is replaced with Q; or N at the 4th position is replaced with ; (iii) Q at the 1st position of light chain CDR3 is E, G, I, M or N; V at the 2nd position is A, D, E, H, L, Q, S or T; V at the 3rd position is I, L, M, N, Q, S or T; L at the 4th position is F, H, I, M, R, S, V, W or Y; S at the 5th position is C, D, E, F, G, H, K, L, N, Q, R, T, V or Y; S at the 6th position is D, E, F, G, H, I, L, M, N, P, Q, R, T, V or Y; P at the 7th position is A, D, E, G, N, Q, S or V; Y in the 8th position is E, F, L, M or Q; or Y in the 9th position is T at position 1 is replaced with D, F, G, I, L, N, S, V, W or Y; (iv) J at position 1 of heavy chain CDR1 is replaced with G or Q; Y at position 2 is replaced with Q; or I at position 4 is replaced with A or Y; (v) the 3rd position of the heavy chain CDR2 is D, E, W or Y; the 5th position is D, H or Y; the 6th position is F, P, W or Y; the G at the 7th position is A, F, L, N or T; the 8th position is F, P, S, T or Y; the T at the 9th position is A, D, E, F, G, H, L, P, S or V; the H at the 10th position is A, D, F, M, R, S, T, V, W or Y; the F at the 11th position is G, H, I , L, M, N, P, Q, V or Y; the S at the 12th position is A, D, G, H, I , L, P, T or V; the A at the 13th position is D, E, F, G, H, I , K, L, M, P, R, S, T, V or Y; R in the 14th position is replaced by A, E, G, H, L, N, P, Q, S, W or Y; F in the 15th position is replaced by D, E, G, L, M, P, R, S, V or W; V in the 16th position is replaced by {A, E, F, G, H, L, R, S, T, V or Y; or G in the 17th position is replaced by E, F, H, L, M, N, P, Q, R, S, T, V or W;Or (vi) in the heavy chain CDR3, G at the 1st position is replaced with E, F, H, N, Q, V or W; J at the 2nd position is replaced with E; O at the 3rd position is replaced with L, Q, T or V; U at the 4th position is replaced with W; F at the 5th position is replaced with L or Y; L at the 6th position is replaced with Q, S or Y; or Y at the 7th position is replaced with C, L, M, N or Y, wherein the light chain CDR1 may include 0 to 5 substitutions, the light chain CDR2 may include 0 to 1 substitution, the light chain CDR3 may include 0 to 7 substitutions, the heavy chain CDR1 may include 0 to 1 substitution, the heavy chain CDR2 may include 0 to 11 substitutions, and the heavy chain CDR3 may include 0 to 6 substitutions.

[0018] In any one of the above

[0013] to

[0017] , the affinity-optimized antibody comprises a light chain CDR1 as described in SEQ ID NO: 1 and any one of SEQ ID NOs: 211 to 250; any one of SEQ ID NO: 2, SEQ ID NOs: 164 to 172, SEQ ID NO: 209 and SEQ ID NO: 210. A light chain variable region comprising a light chain CDR2 as described by one; a light chain CDR3 as described by any one of SEQ ID NO: 3, SEQ ID NOs: 124 to 163, SEQ ID NOs: 173 to 208, and SEQ ID NOs: 251 to 283 and a heavy chain CDR1 as described by any one of SEQ ID NO: 4, and SEQ ID NOs: 90 to 94; a heavy chain CDR2 as described by any one of SEQ ID NO: 5, SEQ ID NOs: 36 to 45, SEQ ID NOs: 54 to 89, and SEQ ID NOs: 100 to 123; and a heavy chain variable region comprising a heavy chain CDR3 as described by any one of SEQ ID NO: 6, SEQ ID NOs: 46 to 53, and SEQ ID NOs: 95 to 99.

[0019] In any one of the above

[0013] to

[0018] , the affinity optimized antibody may comprise a light chain variable region as set forth in any one of SEQ ID NOs: 11 and 288 to 293 and a heavy chain variable region as set forth in any one of SEQ ID NOs: 13 and 284 to 287. [2] In any one of the above

[0013] to

[0019] , the affinity-optimized antibody comprises (a) a light chain variable region as set forth in SEQ ID NO: 11 and a heavy chain variable region as set forth in SEQ ID NO: 284; (b) a light chain variable region as set forth in SEQ ID NO: 11 and a heavy chain variable region as set forth in SEQ ID NO: 287; (c) a light chain variable region as set forth in SEQ ID NO: 292 and a heavy chain variable region as set forth in SEQ ID NO: 13; (d) a light chain variable region as set forth in SEQ ID NO: 290 and a heavy chain variable region as set forth in SEQ ID NO: 287; (e) a light chain variable region as set forth in SEQ ID NO: 288 and a heavy chain variable region as set forth in SEQ ID NO: 285; (f) a light chain variable region as set forth in SEQ ID NO: 289 and a heavy chain variable region as set forth in SEQ ID NO: 286; (g) a light chain variable region as set forth in SEQ ID NO: 290 and a heavy chain variable region as set forth in SEQ ID NO: 286; (h) a light chain variable region as set forth in SEQ ID NO: 291 A light chain variable region and a heavy chain variable region as set forth in SEQ ID NO: 286; (i) a light chain variable region as set forth in SEQ ID NO: 293 and a heavy chain variable region as set forth in SEQ ID NO: 286; or (j) a light chain variable region as set forth in SEQ ID NO: 288 and a heavy chain variable region as set forth in SEQ ID NO: 284.

[0021] In any one of the above [1] to [2], the antibody may further comprise an antibody or an antigen-binding fragment thereof that specifically binds to epidermal growth factor receptor (EGFR).

[0022] In any one of the above [1] to

[0021] , the antibody may be one in which an antibody or an antigen-binding fragment thereof that binds to epidermal growth factor receptor (EGFR) is linked to one end of a light or heavy chain of an antibody that specifically binds c-Met.

[0023] In the above

[0021] or

[0022] , the antigen-binding fragment binding to the EGFR may be Fab, Fab', F(ab')2 or Fv.

[0024] In the above

[0023] , the Fv may be at least one scFv fragment selected from the group consisting of Erbitux, Vectibix, Portrazza, and TheraCIM.

[0025] In the above

[0024] , the Erbitux scFv may include an amino acid sequence described as SEQ ID NO: 295 or SEQ ID NO: 296.

[0026] In the above

[0024] , the Vectibix scFv may include an amino acid sequence described as SEQ ID NO: 297.

[0027] In any one of the above

[0021] to

[0026] , the connection of the antibody or antigen-binding fragment thereof that binds to the EGFR is connected by a connector described in SEQ ID NO: 294. It could be.

[0028] In any one of the above [1] to

[0027] , the antibody or antigen-binding fragment thereof may include a light chain variable region as set forth in SEQ ID NO: 11 and any one of SEQ ID NOs: 288 to 293; and a heavy chain variable region as set forth in any one of SEQ ID NOs: 298 to 312.

[0029] In any one of the above [1] to

[0028] , the antibody or antigen-binding fragment thereof comprises (1) a light chain variable region as set forth in SEQ ID NO: 11 and a heavy chain variable region as set forth in SEQ ID NO: 298; (2) a light chain variable region as set forth in SEQ ID NO: 11 and a heavy chain variable region as set forth in SEQ ID NO: 299; (3) a light chain variable region as set forth in SEQ ID NO: 11 and a heavy chain variable region as set forth in SEQ ID NO: 302; (4) a light chain variable region as set forth in SEQ ID NO: 292 and a heavy chain variable region as set forth in SEQ ID NO: 298; (5) a light chain variable region as set forth in SEQ ID NO: 290 and a heavy chain variable region as set forth in SEQ ID NO: A heavy chain variable region described by SEQ ID NO: 302; (6) a light chain variable region described by SEQ ID NO: 288 and a heavy chain variable region described by SEQ ID NO: 300; (7) a light chain variable region described by SEQ ID NO: 289 and a heavy chain variable region described by SEQ ID NO: 301; (8) a light chain variable region described by SEQ ID NO: 290 and a heavy chain variable region described by SEQ ID NO: 301; (9) a light chain variable region described by SEQ ID NO: 291 and a heavy chain variable region described by SEQ ID NO: 301; (10) a light chain variable region described by SEQ ID NO: 293 and a heavy chain variable region described by SEQ ID NO: 301; (11) a light chain variable region described by SEQ ID NO: 288 and a heavy chain variable region described by SEQ ID NO: 299; (12) a light chain variable region described by SEQ ID NO: 11 and a heavy chain variable region described by SEQ ID NO: 303; (13) a light chain variable region described by SEQ ID NO: 11 and a heavy chain variable region described by SEQ ID NO: 304 Variable region; (14) a light chain variable region described by SEQ ID NO: 11 and a heavy chain variable region described by SEQ ID NO: 307; (15) a light chain variable region described by SEQ ID NO: 292 and a heavy chain variable region described by SEQ ID NO: 303; (16) a light chain variable region described by SEQ ID NO: 290 and a heavy chain variable region described by SEQ ID NO: 307; (17) a light chain variable region described by SEQ ID NO: 288 and a heavy chain variable region described by SEQ ID NO: 305; (18) a light chain variable region described by SEQ ID NO: 289 and a heavy chain variable region described by SEQ ID NO: 306; (19) a light chain variable region described by SEQ ID NO: 290 and a heavy chain variable region described by SEQ ID NO: 306; (20) a light chain variable region described by SEQ ID NO: 291 and a heavy chain variable region described by SEQ ID NO: 306; (21) a light chain variable region described by SEQ ID NO: 293 and a heavy chain variable region described by SEQ ID NO: 306; (22) a light chain variable region described by SEQ ID NO: 288 and a heavy chain variable region described by SEQ ID NO: 304; (23) a light chain variable region described by SEQ ID NO: 11 and a heavy chain variable region described by SEQ ID NO: 308; (24) a light chain variable region described by SEQ ID NO: 11 and a heavy chain variable region described by SEQ ID NO: 309; (25) a light chain variable region described by SEQ ID NO: 11 and a heavy chain variable region described by SEQ ID NO: 312; (26) a light chain variable region described by SEQ ID NO: 292 and a heavy chain variable region described by SEQ ID NO: 308; (27) a light chain variable region described by SEQ ID NO: 290 and a heavy chain variable region described by SEQ ID NO: 312; (28) a light chain variable region described by SEQ ID NO: 288 and a heavy chain variable region described by SEQ ID NO: 310; (29) a light chain variable region described by SEQ ID NO: 289 and a heavy chain variable region described by SEQ ID NO: 311; (30) a light chain variable region described by SEQ ID NO: 290 and a heavy chain variable region described by SEQ ID NO: 311; (31) a light chain variable region described by SEQ ID NO: 291 and a heavy chain variable region described by SEQ ID NO: 311; (32) a sequence number A light chain variable region described by SEQ ID NO: 293 and a heavy chain variable region described by SEQ ID NO: 311; or (33) a light chain variable region described by SEQ ID NO: 288 and a heavy chain variable region described by SEQ ID NO: 309. [3] In any one of the above [1] to

[0029] , the antibody or antigen-binding fragment thereof may comprise a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 11 and a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 308.

[0031] In any one of the above [1] to [3], the antibody or antigen-binding fragment thereof and at least one of drug 1 and drug 2 may be administered simultaneously or separately.

[0032] In any one of the above [1] to

[0031] , the antibody or antigen-binding fragment thereof and at least one of drug 1 and drug 2 may be administered sequentially.

[0033] In any one of the above [1] to

[0032] , the pharmaceutical composition may reduce the size of a tumor.

[0034] In any one of the above [1] to

[0033] , the pharmaceutical composition may increase at least one selected from the group consisting of progression-free survival (PFS), overall survival (OS), complete response rate, and partial response rate of the subject.

[0035] In any one of the above [1] to

[0034] , the antibody or antigen-binding fragment thereof comprises a light chain variable region comprising a light chain CDR1 as set forth in SEQ ID NO: 1; a light chain CDR2 as set forth in SEQ ID NO: 2; a light chain CDR3 as set forth in SEQ ID NO: 3, and a light chain variable region comprising a light chain CDR1 as set forth in SEQ ID NO: 4. A heavy chain variable region comprising a heavy chain CDR1 as described; a heavy chain CDR2 as described as SEQ ID NO: 5; and a heavy chain CDR3 as described as SEQ ID NO: 6, wherein (B) is the drug 1, and the cancer may be gastric cancer.

[0036] In any one of the above [1] to

[0034] , the antibody or antigen-binding fragment thereof comprises a light chain variable region comprising a light chain CDR1 as set forth in SEQ ID NO: 1; a light chain CDR2 as set forth in SEQ ID NO: 2; a light chain CDR3 as set forth in SEQ ID NO: 3; and a heavy chain variable region comprising a heavy chain CDR1 as set forth in SEQ ID NO: 4; a heavy chain CDR2 as set forth in SEQ ID NO: 5; and a heavy chain CDR3 as set forth in SEQ ID NO: 6, wherein (B) is the drug 2, and the cancer may be gastric cancer.

[0037] In any one of the above [1] to

[0036] , the antibody or antigen-binding fragment thereof may comprise a light chain variable region described in SEQ ID NO: 11 and a heavy chain variable region described in SEQ ID NO: 308.

[0038] A pharmaceutical composition for preventing or treating cancer according to the present invention comprises, as an active ingredient, an antibody or an antigen-binding fragment thereof that specifically binds to hepatocyte growth factor receptor (c-Met) that binds to at least one epitope region described in an amino acid sequence selected from the group consisting of (A) SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, and SEQ ID NO: 316, and the pharmaceutical composition may be administered to a subject in combination with (B) at least one of (1) Drug 1 and (2) Drug 2.

[0039] The method for preventing or treating cancer according to the present invention comprises administering to a subject in need of preventing or treating cancer (A) SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315 and SEQ ID NO: A method of treating hepatic cell growth factor receptor (c-Met) comprising administering an antibody or an antigen-binding fragment thereof that specifically binds to hepatocyte growth factor receptor (c-Met) that binds to at least one epitope region described by an amino acid sequence selected from the group consisting of 316, wherein the antibody or antigen-binding fragment thereof may be administered in combination with at least one of (B) (1) Drug 1 and (2) Drug 2. [4] The use of an antibody or an antigen-binding fragment thereof that specifically binds to hepatocyte growth factor receptor (c-Met) that binds to at least one epitope region described in an amino acid sequence selected from the group consisting of (A) SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, and SEQ ID NO: 316 according to the present invention for preventing or treating cancer may be such that the antibody or the antigen-binding fragment thereof is administered in combination with (B) at least one of (1) Drug 1 and (2) Drug 2.

[0041] (A) Use of an antibody or an antigen-binding fragment thereof that specifically binds to hepatocyte growth factor receptor (c-Met) that binds to at least one epitope region described in an amino acid sequence selected from the group consisting of SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, and SEQ ID NO: 316 in the manufacture of a medicament for preventing or treating cancer according to the present invention may be such that the antibody or antibody fragment is administered in combination with (B) at least one of (1) Drug 1 and (2) Drug 2.

[0042] In any one of the above

[0038] to

[0041] , (i) (A) a liver cell growth factor binding to at least one epitope region described by an amino acid sequence selected from the group consisting of SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315 and SEQ ID NO: 316; An antibody or antigen-binding fragment thereof that specifically binds to factor receptor (c-Met), (ii) (B) drug 1, drug 2 or (iii) cancer may be substantially the same as described in [1] to

[0039] above, unless contradictory.

Effect of the invention

Brief description of the drawing

Best mode for carrying out the invention

Form for implementing the invention

【Table 11 Hybridoma light chain CDR

【Table 2 Hybridoma Heavy Chain CDR (3) In vitro tumor cell proliferation inhibition activity of hybridoma c-Met antibody A c-Met specific mouse antibody obtained using a hybridoma cell line, and a chimeric antibody produced by fusing the antibody with human heavy and light chain constant regions Cell proliferation inhibition activity was tested in human gastric cancer cell line MKN45. Specifically, MKN45 (#JCRB0254) cell line was diluted in RPMI-1640 medium (Gibco, #A10491) containing 10% (v / v) FBS and seeded at 2.5 x 10 in each well of a 96-well plate. 3 After dispensing each cell, they were cultured overnight at 37 °C, 5% C02 conditions. After that, the medium in each well of the plate was replaced with 100 seed of RPMI-1640 medium containing 1% (v / v) FBS, and the test antibodies were serially diluted 1 / 10 each to a final concentration of 100 nM to 1 pM (i.e., 100 nM, 10 nM, 1 nM, 100 pM, 10 pM, and 1 pM) and added to each well at 100 M. Then, after the plates were cultured at 37 °C, 5% C02 conditions for 5 days, the medium was removed, and 200 M of TCA (Trichloroacetic acid; Sigma, #T0699) solution was added to each well to fix the cells. The fixed cells were stained for 25 minutes by adding 80 M 0.4% SRB (sulforhodamine B) solution to each well, and then washed five times with 1% acetic acid solution. Then, 150 M 10 mM Tris solution was added to each well of the dried plate to dissolve the SRB dye, and the absorbance was measured at a wavelength of 540 nm using a microplate reader. The results for the MKN45 cell line are shown in Table 3.

Table 3

【Table 4] Consensus sequence for the light and heavy chain variable regions of the 8C4 antibody Example 2. Production of humanized antibody of 8C4 antibody For humanization design of the 8C4 antibody heavy chain, first, Ig Blast (http: / / www.ncbi.nlm.nih.gov / igblast / ) was used to analyze human germline genes that are highly homologous to the heavy chain variable region gene of mouse antibody 8C4. As a result, it was confirmed that IGHV3-23 has 48% homology with 8C4 antibody at the amino acid level, and IGHV3-11 has 46% homology with 8C4 antibody at the amino acid level. CDR-H1, CDR-H2, and CDR— H3 of white mouse antibody 8C4 were defined by Rabat numbering, and hu8C4-1 was produced by designing the CDR portion of mouse antibody 8C4 to be introduced into the framework of IGHV3-23. At this time, 48 (V— I), 49 (S— G), 71 (R— A), Amino acids 73 (N—K), 78 (L—A), and 94 (K—G) are the same as those of the original mouse 8C4 antibody. The heavy chain of hu8C4-1 was finally constructed by back-mutating the amino acid sequence. In the case of hu8C4-2, the CDR portion of the mouse antibody 8C4 was designed to be introduced into the framework of IGHV3-11, and positions 48 (V—I), 49 (S—G), 71 (R—A), 73 (N—K), Amino acids 78 (L—A) and 94 (R—G) were back-mutated to the amino acid sequence of the original mouse 8C4 antibody, ultimately constructing the heavy chain of hu8C4-2. In the case of the 8C4 antibody light chain, for humanization design, human germline genes with high homology to the light chain variable region gene of mouse antibody 8C4 were analyzed through Ig Blast (http: / / www.ncbi .nlm.nih.gov / igblast / ). As a result, it was confirmed that IGKV1-27 had 65.3% homology with 8C4 antibody at the amino acid level, and IGKV1-33 had 64.2% homology with 8C4 antibody at the amino acid level. CDR-L1, CDR-L2, CDR— L3 of the white mouse antibody 8C4 were defined by Rabat numbering, and the CDR portion of the mouse antibody 8C4 was designed to be introduced into the framework of IGKV1-33 to produce hu8C4-1, and was designed to be introduced into the framework of IGKV1-27 to produce hu8C4-2. At this time, both hu8C4-1 and hu8C4-2 had amino acid position 69 (T—R) back-mutated to the amino acid sequence of the original mouse 8C4 antibody. The above 8C4 humanized antibody was expressed in 293T cells using the pCLS05 vector (Korean Patent No. 10-1420274). Specific consensus sequences for the light and heavy chain variable regions of the above hu8C4-l and hu8C4-2 humanized antibodies are shown in Table 5.

Table 5

Table 6

【Table 7]

【Table 8]

【Table 2: List of variable region sequences of light and heavy chain affinity-optimized antibodies The affinity-optimized antibody of the present invention is one that optimizes the affinity of the parent hu8C4 antibody, and all of these were selected based on antigen affinity during the selection process. Therefore, the presented affinity-optimized antibody and antibodies combining the presented heavy and light chain variable region CDRs are all expected to have equivalent effects. For additional experiments, 10 types of affinity-optimized antibodies were produced by combining the light and heavy chain variable regions. Specific light and heavy chain sequence combinations are shown in Table 10.

Table 10

【Table 111

Table 12

Table 13

Table 14

Table 15

Claims

86 【Scope of Claims】 【 Claim 11 (A) an antibody or an antigen-binding fragment thereof that specifically binds to hepatocyte growth factor receptor (c-Met) that binds to at least one epitope region described by an amino acid sequence selected from the group consisting of SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315 and SEQ ID NO: 316, and (B) A pharmaceutical composition for preventing or treating cancer, comprising at least one of (1) drug 1 and (2) drug 2 as an active ingredient: (1) Drug 1: SN-38 represented by the following chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof [Chemical Formula 1] (2) Drug 2: Irinotecan represented by the following chemical formula 2, an optical isomer thereof, or a pharmaceutically acceptable salt thereof [Chemical formula 2] 87 【A pharmaceutical composition according to claim 1, wherein (B) is drug 1. 【

3. A pharmaceutical composition according to claim 2, wherein the cancer is gastric cancer. 【

4. A pharmaceutical composition according to claim 2, wherein the antibody is an antibody comprising a light chain variable region comprising a light chain CDR1 as set forth in SEQ ID NO: 1; a light chain CDR2 as set forth in SEQ ID NO: 2; a light chain CDR3 as set forth in SEQ ID NO: 3; and a heavy chain variable region comprising a heavy chain CDR1 as set forth in SEQ ID NO: 4; a heavy chain CDR2 as set forth in SEQ ID NO: 5; and a heavy chain CDR3 as set forth in SEQ ID NO: 6, or an affinity-optimized antibody thereof. 88

5. In claim 4, the affinity-optimized antibody is an antibody having at least one amino acid sequence substituted in an antibody including a light chain variable region comprising a light chain CDR1 set forth in SEQ ID NO: 1; a light chain CDR2 set forth in SEQ ID NO: 2; a light chain CDR3 set forth in SEQ ID NO: 3; and a heavy chain variable region comprising a heavy chain CDR1 set forth in SEQ ID NO: 4; a heavy chain CDR2 set forth in SEQ ID NO: 5; and a heavy chain CDR3 set forth in SEQ ID NO: 6, wherein (i) G at the 1st position of the light chain CDR1 is A, E, K, L, N, R, S, V or W; A at the 2nd position is C, G, I, P, S, T or V; E at the 3rd position is G, M, N, P, Q, R, S or T; E at the 4th position is A, D, F, G, H, K, M, Q, R, S, T or V; N in the 5th position is A, D, E, G, K, L, P, Q, R, S, T or V; I in the 6th position is A, F, L, M, Q, R, S, T or V; Y in the 7th position is F, H, R or V; or G at the 8th position is replaced with D, F, H, M, N, R, S, T or V; (ii) G at the 1st position of light chain CDR2 is replaced with D, F, H, K, P, Q, S, V or Y; T at the 3rd position is replaced with Q; or N at the 4th position is replaced with G; (iii) Q at the 1st position of light chain CDR3 is replaced with E, G, I, M or N; N at the 2nd position is replaced with A, D, E, H, L, Q, S or T; V at the 3rd position is replaced with I, L, M, N, Q, S or T; L at the 4th position is replaced with F, H, I, M, R, S, V, W or Y; S is C, D, E, F, G, H, K, L, N, Q, R, T, V or Y; S in the 6th position is D, E, F, G, H, I, L, M, N, P, Q, R, T, V or Y; P in the 7th position is A, D, E, G, N, Q, S or V; Y in the 8th position is E, F, L, M or Q; or T in the 9th position is D, F, G, I, L, N, substituted with S, V, W or Y; (iv) the first position of heavy chain CDR1, 日 is G or Q; the second position, Y is Q; or the fourth position, I is A or substituted with 이; (v) the third position of heavy chain CDR2 at position 89, F is D, E, W or Y; at position 5, G is D, H or Y; at position 6, 으 is F, P, W or Y; at position 7, G is A, F, L, N or T; at position 8, N is F, P, S, T or Y; at position 9, T is A, D, E, F, G, H, L, P, S or V; at position 10, H is A, D, F, M, R, S, T, V, W or Y; at position 11, F is G, H, I, L, M, N, P, Q, V or Y; at position 12, ▽} A, D, G, H, I, L, P, T or V; at position 13, A is D, E, F, G, H, I, K, L, M, P, R, S, T, V or Y; at position 14, R is A, E, G, H, L, N, P, Q, S, W or Y; at position 15, F is D, E, G, L, M, P, R, S, V or W; at position 16, 오 is A, E, F, G, H, L, R, S, T, V or Y; or at position 17, G is substituted with E, F, H, L, M, N, P, Q, R, S, T, V or W; or (vi) the first position of heavy chain CDR3, G is E, F, H, N, Q, V or W; the second position, 日 is E; the third position, Y is L, Q, T or V; the fourth position, G is W; the fifth position, F is L or Y; the sixth position, L is Q, S or Y; or the seventh position, Y is substituted with C, L, M, N or 이, wherein the light chain CDR1 has 0 to 5 substitutions, the light chain CDR2 has 0 to 1 substitution, the light chain CDR3 has 0 to 7 substitutions, the heavy chain CDR1 has 0 to 1 substitution, the heavy chain CDR2 has 0 to 11 substitutions, and the heavy chain CDR3 has 0 to 6 substitutions, a pharmaceutical composition. 【

6. A pharmaceutical composition according to claim 2, wherein the antibody further comprises an antibody or an antigen-binding fragment thereof that specifically binds to epidermal growth factor receptor (EGFR). 90

7. A pharmaceutical composition according to claim 2, wherein the antibody or antigen-binding fragment thereof comprises a light chain variable region set forth in SEQ ID NO: 11 and any one of SEQ ID NOs: 288 to 293; and a heavy chain variable region set forth in any one of SEQ ID NOs: 298 to 312. 【

8. A pharmaceutical composition according to claim 2, wherein the antibody or antigen-binding fragment thereof comprises a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 11 and a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO:

308. 【A pharmaceutical composition according to claim 2, wherein the cancer is a cancer that overexpresses c-Met, amplifies c-Met, or activates c-Met.

10. A pharmaceutical composition according to claim 1, wherein (B) is drug 2.

11. A pharmaceutical composition according to claim 10, wherein the cancer is gastric cancer. 【Claim 1 is a pharmaceutical composition according to claim 10, wherein the antibody comprises a light chain variable region comprising a light chain CDR1 as set forth in SEQ ID NO: 1; a light chain CDR2 as set forth in SEQ ID NO: 2; a light chain CDR3 as set forth in SEQ ID NO: 3; and a heavy chain variable region comprising a heavy chain CDR1 as set forth in SEQ ID NO: 4; a heavy chain CDR2 as set forth in SEQ ID NO: 5; and a heavy chain CDR3 as set forth in SEQ ID NO: 6; or an affinity-optimized antibody thereof.

13. The affinity-optimized antibody of claim 12, wherein the affinity-optimized antibody comprises a light chain variable region comprising a light chain CDR1 set forth in SEQ ID NO: 1; a light chain CDR2 set forth in SEQ ID NO: 2; a light chain CDR3 set forth in SEQ ID NO: 3; and a heavy chain variable region comprising a heavy chain CDR1 set forth in SEQ ID NO: 4; a heavy chain CDR2 set forth in SEQ ID NO: 5; and a heavy chain CDR3 set forth in SEQ ID NO: 6, wherein at least one amino acid sequence is substituted in an antibody, wherein (i) G at the 1st position of the light chain CDR1 is A, E, K, L, N, R, S, V or W; A at the 2nd position is C, G, I, P, S, T or V; S at the 3rd position is G, M, N, P, Q, R, S or T; E at the 4th position is A, D, F, G, H, K, M, Q, R, S, T or V; N at the 5th position is A, D, E, G, K, L, P, Q, R, S, T or V; I in the 6th position is A, F, L, M, Q, R, S, T or V; Y in the 7th position is F, H, R or V; or G in the 8th position is D, F, H, M, N, R, S, T or 92 V is substituted; (ii) G at position 1 of light chain CDR2 is substituted with D, F, H, K, P, Q, S, V or Y; T at position 3 is substituted with Q; or N at position 4 is substituted with ; ( iii ) Q at the 1st position of light chain CDR3 is E, G, I, M or N; V at the 2nd position is A, D, E, H, L, Q, S or T; V at the 3rd position is I, L, M, N, Q, S or T; L at the 4th position is F, H, I, M, R, S, V, W or Y; S at the 5th position is C, D, E, F, G, H, K, L, N, Q, R, T, V or Y; S at the 6th position is D, E, F, G, H, I, L, M, N, P, Q, R, T, V or Y; P at the 7th position is A, D, E, G, N, Q, S or V; Y at the 8th position is E, F, L, M or Q; or T at the 9th position is replaced by D, F, G, I, L, N, S, V, W or Y; (iv) 日 at the 1st position of the heavy chain CDR1 is G or Q; Y at the 2nd position is Q; or I at the 4th position is replaced by A or 이; (v) 도 at the 3rd position of the heavy chain CDR2 is D, E, W or Y; 으 at the 5th position is D, H or Y; 으 at the 6th position is F, P, W or Y; G at the 7th position is A, F, L, N or T; 凡 at the 8th position is F, P, S, T or Y; T at the 9th position is A, D, E, F, G, H, L, P, S or V; H at the 10th position is A, D, F, M, R, S, T, V, W or Y; F at the 11th position is G, H, I, L, M, N, P, Q, V or Y; S at the 12th position is A, D, G, H, I, L, P, T or V; A at the 13th position is D, E, F, G, H, I, K, L, M, P, R, S, T, V or Y; R at the 14th position is A, E, G, H, L, N, P, Q, S, W or Y; F at the 15th position is D, E, G, L, M, P, R, S, V or W; V at the 16th position} A, E, F, G, H, L, R, S, T, V or Y; or G at the 17th position is replaced by E, F, H, L, M, N, P, Q, R, S, T, V or W; or (vi) G at the 1st position of the heavy chain CDR3 is E, F, H, N, Q, V or W; 日 at the 2nd position is E; 오 at the 3rd position is L, Q, T or V; 으 at the 4th position is W; F at the 5th position is L or 93 Y; L at the 6th position is replaced with Q, S or Y; or Y at the 7th position is replaced with C, L, M, N or this, wherein the light chain CDR1 comprises 0 to 5 substitutions, the light chain CDR2 comprises 0 to 1 substitution, the light chain CDR3 comprises 0 to 7 substitutions, the heavy chain CDR1 comprises 0 to 1 substitution, the heavy chain CDR2 comprises 0 to 11 substitutions, and the heavy chain CDR3 comprises 0 to 6 substitutions.

14. A pharmaceutical composition according to claim 10, wherein the antibody further comprises an antibody or an antigen-binding fragment thereof that specifically binds to epidermal growth factor receptor (EGFR).

15. A pharmaceutical composition according to claim 10, wherein the antibody or antigen-binding fragment thereof comprises a light chain variable region set forth in SEQ ID NO: 11 and any one of SEQ ID NOs: 288 to 293; and a heavy chain variable region set forth in any one of SEQ ID NOs: 298 to 312.

16. A pharmaceutical composition according to claim 10, wherein the antibody or antigen-binding fragment thereof comprises a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 11 and a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO:

308.

17. A pharmaceutical composition according to claim 10, wherein the cancer is a cancer that overexpresses c-Met, amplifies c-Met, or activates c-Met.

18. (A) A pharmaceutical composition for the prevention or treatment of cancer, comprising as an active ingredient an antibody or an antigen-binding fragment thereof that specifically binds to hepatocyte growth factor receptor (c-Met) that binds to at least one epitope region described in an amino acid sequence selected from the group consisting of SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, and SEQ ID NO: 316, wherein the pharmaceutical composition is administered to a subject in combination with (B) at least one of the following (1) Drug 1 and (2) Drug 2: (1) Drug 1: SN-38 represented by the following chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof [Chemical Formula 1] (2) Drug 2: Irinotecan represented by the following chemical formula 2, Optical isomer or pharmaceutically acceptable salt thereof [Chemical formula 2] 【Claim 1: A pharmaceutical composition according to claim 18, wherein (B) is drug 1. 【

20. A pharmaceutical composition according to claim 19, wherein the cancer is gastric cancer. 【

21. In claim 19, the antibody comprises a light chain variable region comprising a light chain CDR1 as set forth in SEQ ID NO: 1; a light chain CDR2 as set forth in SEQ ID NO: 2; a light chain CDR3 as set forth in SEQ ID NO: 3; and a heavy chain variable region comprising a heavy chain CDR1 as set forth in SEQ ID NO: 4; a heavy chain CDR2 as set forth in SEQ ID NO: 5; and a heavy chain CDR3 as set forth in SEQ ID NO:

6. A pharmaceutical composition comprising 96 or an affinity-optimized antibody thereof. 【Claim 2 The antibody of claim 21, wherein the affinity-optimized antibody comprises a light chain variable region comprising a light chain CDR1 set forth in SEQ ID NO: 1; a light chain CDR2 set forth in SEQ ID NO: 2; a light chain CDR3 set forth in SEQ ID NO: 3; and a heavy chain variable region comprising a heavy chain CDR1 set forth in SEQ ID NO: 4; a heavy chain CDR2 set forth in SEQ ID NO: 5; and a heavy chain CDR3 set forth in SEQ ID NO: 6, wherein at least one amino acid sequence is substituted in an antibody, wherein (i) G at the 1st position of the light chain CDR1 is A, E, K, L, N, R, S, V or W; A at the 2nd position is C, G, I, P, S, T or V; S at the 3rd position is G, M, N, P, Q, R, S or T; E at the 4th position is A, D, F, G, H, K, M, Q, R, S, T or V; N at the 5th position is A, D, E, G, K, L, P, Q, R, S, T or V; I at position 6 is replaced by A, F, L, M, Q, R, S, T or V; Y at position 7 is replaced by F, H, R or V; or G at position 8 is replaced by D, F, H, M, N, R, S, T or V; (ii) G at position 1 of light chain CDR2 is replaced by D, F, H, K, P, Q, S, V or Y; T at position 3 is replaced by Q; or N at position 4 is replaced by ; (iii) Q at the 1st position of light chain CDR3 is E, G, I, M or N; V at the 2nd position is A, D, E, H, L, Q, S or T; V at the 3rd position is I, L, M, N, Q, S or T; L at the 4th position is F, H, I, M, R, S, V, W or Y; S at the 5th position is C, D, E, F, G, H, K, L, N, Q, R, T, V or Y; S at the 6th position is D, E, F, G, H, I, L, M, N, P, Q, R, T, V or Y; P at the 7th position is A, D, E, G, N, Q, S or V; Y in the 8th position is E, F, L, M or Q; or Y in the 9th position is T at position 97 is replaced with D, F, G, I, L, N, S, V, W or Y; (iv) J at position 1 of heavy chain CDR1 is replaced with G or Q; Y at position 2 is replaced with Q; or I at position 4 is replaced with A or Y; (v) the 3rd position of the heavy chain CDR2 is D, E, W or Y; the 5th position is D, H or Y; the 6th position is F, P, W or Y; the G at the 7th position is A, F, L, N or T; the 8th position is F, P, S, T or Y; the T at the 9th position is A, D, E, F, G, H, L, P, S or V; the H at the 10th position is A, D, F, M, R, S, T, V, W or Y; the F at the 11th position is G, H, I , L, M, N, P, Q, V or Y; the S at the 12th position is A, D, G, H, I , L, P, T or V; the A at the 13th position is D, E, F, G, H, I , K, L, M, P, R, S, T, V or Y; R in the 14th position is replaced by A, E, G, H, L, N, P, Q, S, W or Y; F in the 15th position is replaced by D, E, G, L, M, P, R, S, V or W; V in the 16th position is replaced by {A, E, F, G, H, L, R, S, T, V or Y; or G in the 17th position is replaced by E, F, H, L, M, N, P, Q, R, S, T, V or W;or (vi) a pharmaceutical composition wherein G at position 1 of heavy chain CDR3 is replaced with E, F, H, N, Q, V or W; J at position 2 is replaced with E; O at position 3 is replaced with L, Q, T or V; U at position 4 is replaced with W; F at position 5 is replaced with L or Y; L at position 6 is replaced with Q, S or Y; or Y at position 7 is replaced with C, L, M, N or Y, wherein light chain CDR1 comprises 0 to 5 substitutions, light chain CDR2 comprises 0 to 1 substitution, light chain CDR3 comprises 0 to 7 substitutions, heavy chain CDR1 comprises 0 to 1 substitution, heavy chain CDR2 comprises 0 to 11 substitutions, and heavy chain CDR3 comprises 0 to 6 substitutions. 【

23. In claim 19, the antibody further binds to epidermal growth factor receptor (EGFR). A pharmaceutical composition further comprising a specifically binding antibody or antigen-binding fragment thereof.

24. A pharmaceutical composition according to claim 19, wherein the antibody or antigen-binding fragment thereof comprises a light chain variable region set forth in SEQ ID NO: 11 and any one of SEQ ID NOs: 288 to 293; and a heavy chain variable region set forth in any one of SEQ ID NOs: 298 to 312. 【

25. A pharmaceutical composition according to claim 19, wherein the antibody or antigen-binding fragment thereof comprises a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 11 and a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO:

308. 【

26. A pharmaceutical composition according to claim 19, wherein the cancer is a cancer that overexpresses c-Met, amplifies c-Met, or activates c-Met. 【

27. ​​A pharmaceutical composition according to claim 18, wherein (B) is drug 2. 99

28. A pharmaceutical composition according to claim 27, wherein the cancer is gastric cancer. 【 A pharmaceutical composition according to claim 2, wherein the antibody is an antibody comprising a light chain variable region comprising a light chain CDR1 as set forth in SEQ ID NO: 1; a light chain CDR2 as set forth in SEQ ID NO: 2; a light chain CDR3 as set forth in SEQ ID NO: 3; and a heavy chain variable region comprising a heavy chain CDR1 as set forth in SEQ ID NO: 4; a heavy chain CDR2 as set forth in SEQ ID NO: 5; and a heavy chain CDR3 as set forth in SEQ ID NO: 6, or an affinity-optimized antibody thereof. 【

30. The antibody of claim 29, wherein the affinity-optimized antibody comprises a light chain variable region comprising a light chain CDR1 set forth in SEQ ID NO: 1; a light chain CDR2 set forth in SEQ ID NO: 2; a light chain CDR3 set forth in SEQ ID NO: 3; and a heavy chain variable region comprising a heavy chain CDR1 set forth in SEQ ID NO: 4; a heavy chain CDR2 set forth in SEQ ID NO: 5; and a heavy chain CDR3 set forth in SEQ ID NO: 6, wherein at least one amino acid sequence is substituted in an antibody, wherein (i) G at the 1st position of the light chain CDR1 is A, E, K, L, N, R, S, V or W; A at the 2nd position is C, G, I, P, S, T or V; S at the 3rd position is G, M, N, P, Q, R, S or T; E at the 4th position is A, D, F, G, H, K, M, Q, R, S, T or V; N at the 5th position is A, D, E, G, K, L, 100 P, Q, R, S, T or V; I at position 6 is replaced with A, F, L, M, Q, R, S, T or V; Y at position 7 is replaced with F, H, R or V; or G at position 8 is replaced with D, F, H, M, N, R, S, T or V; (ii) G at position 1 of light chain CDR2 is replaced with D, F, H, K, P, Q, S, V or Y; T at position 3 is replaced with Q; or N at position 4 is replaced with ; ( iii ) Q at the 1st position of light chain CDR3 is E, G, I, M or N; V at the 2nd position is A, D, E, H, L, Q, S or T; V at the 3rd position is I, L, M, N, Q, S or T; L at the 4th position is F, H, I, M, R, S, V, W or Y; S at the 5th position is C, D, E, F, G, H, K, L, N, Q, R, T, V or Y; S at the 6th position is D, E, F, G, H, I, L, M, N, P, Q, R, T, V or Y; P at the 7th position is A, D, E, G, N, Q, S or V; Y at the 8th position is replaced by E, F, L, M or Q; or T at the 9th position is replaced by D, F, G, I, L, N, S, V, W or Y; (iv) 日 at the 1st position of the heavy chain CDR1 is replaced by G or Q; Y at the 2nd position is replaced by Q; or I at the 4th position is replaced by A or 이; (v) 도 at the 3rd position of the heavy chain CDR2 is replaced by D, E, W or Y; 으 at the 5th position is replaced by D, H or Y; 으 at the 6th position is replaced by F, P, W or Y; G at the 7th position is replaced by A, F, L, N or T; 凡 at the 8th position is replaced by F, P, S, T or Y; T at the 9th position is replaced by A, D, E, F, G, H, L, P, S or V; H at the 10th position is replaced by A, D, F, M, R, S, T, V, W or Y; F at the 11th position is replaced by G, H, I, L, M, N, P, Q, V or Y; S at the 12th position is replaced by A, D, G, H, I, L, P, T or V; A at the 13th position is replaced by D, E, F, G, H, I, K, L, M, P, R, S, T, V or Y; R at the 14th position is replaced by A, E, G, H, L, N, P, Q, S, W or Y; F at the 15th position is replaced by D, E, G, L, M, P, R, S, V or W; V at the 16th position} A, E, F, G, H, L, R, S, T, V or Y; or G at the 17th position is replaced by E, F, H, L, M, N, P, Q, R, S, T, V or W; or 101 (vi) A pharmaceutical composition wherein G at position 1 of heavy chain CDR3 is replaced with E, F, H, N, Q, V or W; J at position 2 is replaced with E; O at position 3 is replaced with L, Q, T or V; U at position 4 is replaced with W; F at position 5 is replaced with L or Y; L at position 6 is replaced with Q, S or Y; or Y at position 7 is replaced with C, L, M, N or Y, wherein light chain CDR1 comprises 0 to 5 substitutions, light chain CDR2 comprises 0 to 1 substitution, light chain CDR3 comprises 0 to 7 substitutions, heavy chain CDR1 comprises 0 to 1 substitution, heavy chain CDR2 comprises 0 to 11 substitutions, and heavy chain CDR3 comprises 0 to 6 substitutions. 【

31. A pharmaceutical composition according to claim 27, wherein the antibody further comprises an antibody or an antigen-binding fragment thereof that specifically binds to epidermal growth factor receptor (EGFR). 【Claim 3 A pharmaceutical composition according to claim 27, wherein the antibody or antigen-binding fragment thereof comprises a light chain variable region set forth in SEQ ID NO: 11 and any one of SEQ ID NOs: 288 to 293; and a heavy chain variable region set forth in any one of SEQ ID NOs: 298 to 312. 【

33. In claim 27, the antibody or antigen-binding fragment thereof has the sequence number 11. A pharmaceutical composition comprising a light chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 102 and a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO:

308.

34. A pharmaceutical composition according to claim 27, wherein the cancer is a cancer that overexpresses c-Met, amplifies c-Met, or activates c-Met.

35. A method for preventing or treating cancer, comprising the step of administering to a subject in need of prevention or treatment of cancer (A) an antibody or an antigen-binding fragment thereof that specifically binds to hepatocyte growth factor receptor (c-Met) that binds to at least one epitope region described in an amino acid sequence selected from the group consisting of SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, and SEQ ID NO: 316, wherein the antibody or antigen-binding fragment thereof is administered in combination with (B) at least one of the following (1) Drug 1 and (2) Drug 2: (1) Drug 1: SN-38 represented by the following chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof [Chemical Formula 1] 103 (2) Drug 2: Irinotecan represented by the following chemical formula 2, an optical isomer thereof, or a pharmaceutically acceptable salt thereof [Chemical formula 2]

36. (A) An antibody or antigen-binding fragment thereof that specifically binds to hepatocyte growth factor receptor (c-Met) that binds to at least one epitope region described in an amino acid sequence selected from the group consisting of SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315, and SEQ ID NO: 316, for use in preventing or treating cancer, wherein the antibody or antigen-binding fragment thereof is used in combination with at least one of (1) Drug 1 and (2) Drug 2 below. 104 administered, intended for: (1) Drug 1: SN-38 represented by the following chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof [Chemical Formula 1] (2) Drug 2: Irinotecan represented by the following chemical formula 2, an optical isomer thereof, or a pharmaceutically acceptable salt thereof [Chemical formula 2] 【

37. (A) in the manufacture of a medicament for use in preventing or treating cancer 105 Use of an antibody or an antigen-binding fragment thereof that specifically binds to hepatocyte growth factor receptor (c-Met) that binds to at least one epitope region as described by an amino acid sequence selected from the group consisting of SEQ ID NO: 313, SEQ ID NO: 314, SEQ ID NO: 315 and SEQ ID NO: 316, wherein the antibody or antibody fragment is (B) administered in combination with at least one of the following (1) Drug 1 and (2) Drug 2: (1) Drug 1: SN-38 represented by the following chemical formula 1, an optical isomer thereof, or a pharmaceutically acceptable salt thereof [Chemical Formula 1] (2) Drug 2: Irinotecan represented by the following chemical formula 2, an optical isomer thereof, or a pharmaceutically acceptable salt thereof [Chemical formula 2] 106

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