JP2020522555A5 - - Google Patents

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JP2020522555A5
JP2020522555A5 JP2019567709A JP2019567709A JP2020522555A5 JP 2020522555 A5 JP2020522555 A5 JP 2020522555A5 JP 2019567709 A JP2019567709 A JP 2019567709A JP 2019567709 A JP2019567709 A JP 2019567709A JP 2020522555 A5 JP2020522555 A5 JP 2020522555A5
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antigen
antibody
binding fragment
icos
binding portion
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Priority claimed from PCT/IB2018/054167 external-priority patent/WO2018225033A1/en
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統計学的解析
一元配置分散分析またはスチューデントt検定を、図面凡例中で特定される通りに用いた。データは、GraphPad Prismソフトウェア（GraphPad社）を用いて解析し、0.05未満のp値を統計学的に有意であると見なした。（* P≦0.05；** P≦0.01；*** P≦0.005；**** P＜0.0001）。
本発明は以下を提供する。
１． 有効量のヒトICOSを標的とする薬剤および有効量のヒトPD1またはヒトPD-L1を標的とする薬剤を患者に逐次的に投与するステップを含む、それを必要とする患者での癌を治療する方法であって、ヒトICOSを標的とする薬剤の投与に続いて、ヒトPD1またはヒトPD-L1を標的とする薬剤を投与する、上記方法。
２． ヒトICOSを標的とする薬剤が、抗ICOS抗体またはその抗原結合性部分である、上記1に記載の方法。
３． 抗ICOS抗体が、ICOSアゴニストである、上記2に記載の方法。
４． 抗ICOS抗体が、配列番号7で表わされるアミノ酸配列に対して少なくとも90％同一なアミノ酸配列を含むVHドメイン、および配列番号8で表わされるアミノ酸配列に対して少なくとも90％同一なアミノ酸配列を含むVLドメインを含む、上記2または3に記載の方法。
５． 抗ICOS抗体が、配列番号7で表わされるアミノ酸配列を含むVHドメイン、および配列番号8で表わされるアミノ酸配列を含むVLドメインを含む、上記2〜4のいずれかに記載の方法。
６． ヒトPD1を標的とする薬剤が、抗PD1抗体またはその抗原結合性部分である、上記1に記載の方法。
７． 抗PD1抗体が、PD1アンタゴニストである、上記6に記載の方法。
８． 抗PD1抗体が、ペンブロリズマブである、上記6または7に記載の方法。
９． 抗PD1抗体が、ニボルマブである、上記6または7に記載の方法。
１０． ヒトPD-L1を標的とする薬剤が、抗PD-L1抗体またはその抗原結合性部分である、上記1に記載の方法。
１１． 抗PD-L1抗体が、PD1アンタゴニストである、上記10に記載の方法。
１２． ヒトICOSを標的とする薬剤、または抗ICOS抗体もしくはその抗原結合性部分が、週1回、2週間に1回、3週間に1回、または4週間に1回投与される、上記1〜11のいずれかに記載の方法。
１３． ヒトPD1もしくはヒトPD-L1を標的とする薬剤、または抗PD1抗体もしくはその抗原結合性部分、または抗PD-L1抗体もしくはその抗原結合性部分が、週1回、2週間に1回、3週間に1回、または4週間に1回投与される、上記1〜12のいずれかに記載の方法。
１４． 癌が、結腸直腸癌（CRC）、胃癌、食道癌、子宮頸癌、膀胱癌、乳癌、頭頚部癌、卵巣癌、黒色腫、腎細胞癌（RCC）、EC扁平上皮癌、非小細胞肺癌、中皮腫、膵臓癌、および前立腺癌からなる群より選択される、上記1〜13のいずれかに記載の方法。
１５． ヒトICOSを標的とする薬剤、または抗ICOS抗体もしくはその抗原結合性部分が、静脈内（IV）注入として投与される、上記1〜14のいずれかに記載の方法。
１６． ヒトPD1もしくはヒトPDL1を標的とする薬剤、または抗PD1抗体もしくはその抗原結合性部分、または抗PDL1抗体もしくはその抗原結合性部分が、静脈内（IV）注入として投与される、上記26〜33のいずれかに記載の方法。
１７． ヒトPD1もしくはヒトPDL1を標的とする薬剤、または抗PD1抗体もしくはその抗原結合性部分、または抗PDL1抗体もしくはその抗原結合性部分の投与開始が、ヒトICOSを標的とする薬剤、または抗ICOS抗体もしくはその抗原結合性部分の投与開始の1週間後、2週間後、3週間後、および4週間後から選択される時点で開始される、上記1〜16のいずれかに記載の方法。
１８． ヒトICOSを標的とする薬剤、または抗ICOS抗体もしくはその抗原結合性部分、およびヒトPD1もしくはヒトPDL1を標的とする薬剤、または抗PD1抗体もしくはその抗原結合性部分、または抗PDL1抗体もしくはその抗原結合性部分が、前記ヒトが疾患進行または許容不能な毒性を示すまで、該ヒトに対して投与される、上記1〜17のいずれかに記載の方法。
１９． それを必要とするヒトでの癌の治療での逐次的使用のための、抗ICOS抗体またはその抗原結合性断片、および抗PD1抗体またはその抗原結合性断片であって、抗ICOS抗体の投与に続いて、抗PD1抗体が投与される、上記抗体またはその抗原結合性断片。
２０． それを必要とするヒトでの癌の治療での逐次的使用のための、抗ICOS抗体またはその抗原結合性断片、および抗PD-L1抗体またはその抗原結合性断片であって、抗ICOS抗体の投与に続いて、抗PD-L1抗体が投与される、上記抗体またはその抗原結合性断片。
２１． PD-1アンタゴニストである、上記15または16に記載の抗PD1抗体または抗PD-L1抗体。
２２． ペンブロリズマブである、上記19または21に記載の抗PD1抗体。
２３． ニボルマブである、上記19または21に記載の抗PD1抗体。
２４． ICOSを標的とするアゴニスト抗体である、上記19〜23のいずれかに記載の抗ICOS抗体。
２５． 配列番号7で表わされるアミノ酸配列に対して少なくとも90％同一なアミノ酸配列を含むVHドメイン、および配列番号8で表わされるアミノ酸配列に対して少なくとも90％同一なアミノ酸配列を含むVLドメインを含む、上記19〜24のいずれかに記載の抗ICOS抗体。
２６． 配列番号7で表わされるアミノ酸配列を含むVHドメイン、および配列番号8で表わされるアミノ酸配列を含むVLドメインを含む、上記19〜25のいずれかに記載の抗ICOS抗体。
２７． 週1回、2週間に1回、3週間に1回、または4週間に1回投与される、上記19〜26のいずれかに記載の抗ICOS抗体。
２８． 週1回、2週間に1回、3週間に1回、または4週間に1回投与される、上記19〜27のいずれかに記載の抗PD1抗体または抗PD-L1抗体。
２９． 癌が、結腸直腸癌（CRC）、胃癌、食道癌、子宮頸癌、膀胱癌、乳癌、頭頚部癌、卵巣癌、黒色腫、腎細胞癌（RCC）、EC扁平上皮癌、非小細胞肺癌、中皮腫、膵臓癌、および前立腺癌からなる群より選択される、上記19および21〜28のいずれかに記載の抗ICOS抗体および抗PD1抗体、または上記20〜29のいずれかに記載の抗ICOS抗体および抗PD-L1抗体。
３０． 癌の治療のための医薬の製造での、抗ICOS抗体またはその抗原結合性部分および抗PD1抗体またはその抗原結合性部分の使用であって、抗ICOS抗体またはその抗原結合性部分および抗PD1抗体またはその抗原結合性部分が逐次的に投与され、かつ抗ICOS抗体またはその抗原結合性部分の投与に続いて抗PD1抗体またはその抗原結合性部分が投与される、上記使用。
３１． 癌の治療のための医薬の製造での、抗ICOS抗体またはその抗原結合性部分および抗PDL1抗体またはその抗原結合性部分の使用であって、抗ICOS抗体またはその抗原結合性部分および抗PDL1抗体またはその抗原結合性部分が逐次的に投与され、かつ抗ICOS抗体またはその抗原結合性部分の投与に続いて抗PDL1抗体またはその抗原結合性部分が投与される、上記使用。
３２． 抗ICOS抗体またはその抗原結合性部分をコードするポリヌクレオチドであって、抗ICOS抗体またはその抗原結合性部分が、抗PD1抗体またはその抗原結合性部分と共に、癌患者に対して逐次的に投与され、かつ抗ICOS抗体またはその抗原結合性部分の投与に続いて抗PD1抗体またはその抗原結合性部分が投与される、上記ポリヌクレオチド。
３３． 抗ICOS抗体またはその抗原結合性部分をコードするポリヌクレオチドであって、抗ICOS抗体またはその抗原結合性部分が、抗PDL1抗体またはその抗原結合性部分と共に、癌患者に対して逐次的に投与され、かつ抗ICOS抗体またはその抗原結合性部分の投与に続いて抗PDL1抗体またはその抗原結合性部分が投与される、上記ポリヌクレオチド。
３４． 抗PD1抗体またはその抗原結合性部分をコードするポリヌクレオチドであって、抗PD1抗体またはその抗原結合性部分が、抗ICOS抗体またはその抗原結合性部分と共に、癌患者に対して逐次的に投与され、かつ抗ICOS抗体またはその抗原結合性部分の投与に続いて抗PD1抗体またはその抗原結合性部分が投与される、上記ポリヌクレオチド。
３５． 抗PDL1抗体またはその抗原結合性部分をコードするポリヌクレオチドであって、抗PDL1抗体またはその抗原結合性部分が、抗ICOS抗体またはその抗原結合性部分と共に、癌患者に対して逐次的に投与され、かつ抗ICOS抗体またはその抗原結合性部分の投与に続いて抗PDL1抗体またはその抗原結合性部分が投与される、上記ポリヌクレオチド。
３６． 上記32〜35のいずれかに記載のポリヌクレオチドを含むベクター。
３７． 上記36に記載のベクターを含む宿主細胞。
３８． 抗ICOS抗体またはその抗原結合性部分の作製方法であって、
(a) 抗ICOS抗体またはその抗原結合性部分を発現するために好適な条件下で上記32または33に記載のポリヌクレオチドを含む宿主細胞を培養するステップ；および
(b) 抗ICOS抗体またはその抗原結合性部分を単離するステップ
を含む、上記方法。
３９． 抗PD1抗体またはその抗原結合性部分の作製方法であって、
(a) 抗PD1抗体またはその抗原結合性部分を発現するために好適な条件下で上記34に記載のポリヌクレオチドを含む宿主細胞を培養するステップ；および
(b) 抗PD1抗体またはその抗原結合性部分を単離するステップ
を含む、上記方法。
４０． 抗PDL1抗体またはその抗原結合性部分の作製方法であって、
(a) 抗PDL1抗体またはその抗原結合性部分を発現するために好適な条件下で上記35に記載のポリヌクレオチドを含む宿主細胞を培養するステップ；および
(b) 抗PDL1抗体またはその抗原結合性部分を単離するステップ
を含む、上記方法。 Statistical analysis One-way ANOVA or Student's t-test was used as specified in the drawing legend. The data were analyzed using GraphPad Prism software (GraphPad) and p-values less than 0.05 were considered statistically significant. ( * P ≤ 0.05; ** P ≤ 0.01; *** P ≤ 0.005; **** P <0.0001).
The present invention provides:
1. 1. Treating cancer in patients who require it, including the step of sequentially administering to the patient an effective amount of a drug that targets human ICOS and an effective amount of a drug that targets human PD1 or human PD-L1. The method described above, wherein the administration of a drug targeting human ICOS is followed by the administration of a drug targeting human PD1 or human PD-L1.
2. The method according to 1 above, wherein the drug targeting human ICOS is an anti-ICOS antibody or an antigen-binding portion thereof.
3. 3. The method according to 2 above, wherein the anti-ICOS antibody is an ICOS agonist.
4. The anti-ICOS antibody contains a VH domain containing at least 90% identical amino acid sequence to the amino acid sequence represented by SEQ ID NO: 7, and an amino acid sequence containing at least 90% identical to the amino acid sequence represented by SEQ ID NO: 8. The method according to 2 or 3 above, including the VL domain.
5. The method according to any one of 2 to 4 above , wherein the anti-ICOS antibody comprises a V H domain containing the amino acid sequence represented by SEQ ID NO: 7 and a VL domain containing the amino acid sequence represented by SEQ ID NO: 8.
6. The method according to 1 above, wherein the drug that targets human PD1 is an anti-PD1 antibody or an antigen-binding portion thereof.
7. The method according to 6 above, wherein the anti-PD1 antibody is a PD1 antagonist.
8. The method according to 6 or 7 above, wherein the anti-PD1 antibody is pembrolizumab.
9. The method according to 6 or 7 above, wherein the anti-PD1 antibody is nivolumab.
10. The method according to 1 above, wherein the drug that targets human PD-L1 is an anti-PD-L1 antibody or an antigen-binding portion thereof.
11. The method according to 10 above, wherein the anti-PD-L1 antibody is a PD1 antagonist.
12. Drugs targeting human ICOS, or anti-ICOS antibodies or antigen-binding portions thereof, are administered once a week, once every two weeks, once every three weeks, or once every four weeks, 1 to 11 above. The method described in any of.
13. Drugs that target human PD1 or human PD-L1, or anti-PD1 antibody or antigen-binding portion thereof, or anti-PD-L1 antibody or antigen-binding portion thereof, once a week, once every two weeks, for three weeks The method according to any one of 1 to 12 above, which is administered once in 1 or once every 4 weeks.
14. Cancers include colorectal cancer (CRC), gastric cancer, esophageal cancer, cervical cancer, bladder cancer, breast cancer, head and neck cancer, ovarian cancer, melanoma, renal cell cancer (RCC), EC squamous cell carcinoma, non-small cell lung cancer The method according to any one of 1 to 13 above, which is selected from the group consisting of mesopharyngeal carcinoma, pancreatic cancer, and prostate cancer.
15. The method according to any one of 1 to 14 above, wherein a drug targeting human ICOS, or an anti-ICOS antibody or antigen-binding portion thereof, is administered as an intravenous (IV) infusion.
16. Drugs targeting human PD1 or human PDL1, or anti-PD1 antibody or antigen-binding portion thereof, or anti-PDL1 antibody or antigen-binding portion thereof, are administered as intravenous (IV) infusions, 26-33 above. The method described in either.
17. A drug that targets human PD1 or human PDL1, or an anti-PD1 antibody or antigen-binding portion thereof, or an anti-PDL1 antibody or a drug that targets human ICOS or an anti-ICOS antibody or The method according to any one of 1 to 16 above, which is started at a time selected from 1 week, 2 weeks, 3 weeks, and 4 weeks after the start of administration of the antigen-binding portion.
18. A drug that targets human ICOS, or an anti-ICOS antibody or antigen-binding portion thereof, and a drug that targets human PD1 or human PDL1, or an anti-PD1 antibody or antigen-binding portion thereof, or an anti-PDL1 antibody or antigen-binding portion thereof. The method according to any of 1 to 17 above, wherein the sex moiety is administered to the human until the human exhibits disease progression or unacceptable toxicity.
19. Anti-ICOS antibody or antigen-binding fragment thereof, and anti-PD1 antibody or antigen-binding fragment thereof for sequential use in the treatment of cancer in humans who require it, for administration of anti-ICOS antibody. The antibody or antigen-binding fragment thereof to which the anti-PD1 antibody is subsequently administered.
20. Anti-ICOS antibody or antigen-binding fragment thereof, and anti-PD-L1 antibody or antigen-binding fragment thereof for sequential use in the treatment of cancer in humans in need thereof, of the anti-ICOS antibody. The antibody or antigen-binding fragment thereof to which an anti-PD-L1 antibody is administered following administration.
21. The anti-PD1 antibody or anti-PD-L1 antibody according to 15 or 16 above, which is a PD-1 antagonist.
22. The anti-PD1 antibody according to 19 or 21 above, which is pembrolizumab.
23. The anti-PD1 antibody according to 19 or 21 above, which is nivolumab.
24. The anti-ICOS antibody according to any one of 19 to 23 above, which is an agonist antibody that targets ICOS.
25. Includes a V H domain containing at least 90% identical amino acid sequence to the amino acid sequence represented by SEQ ID NO: 7 and a V L domain containing at least 90% identical amino acid sequence to the amino acid sequence represented by SEQ ID NO: 8. , The anti-ICOS antibody according to any one of 19 to 24 above.
26. The anti-ICOS antibody according to any one of 19 to 25 above , which comprises a V H domain containing the amino acid sequence represented by SEQ ID NO: 7 and a VL domain containing the amino acid sequence represented by SEQ ID NO: 8.
27. The anti-ICOS antibody according to any one of 19 to 26 above, which is administered once a week, once every two weeks, once every three weeks, or once every four weeks.
28. The anti-PD1 antibody or anti-PD-L1 antibody according to any one of 19 to 27 above, which is administered once a week, once every two weeks, once every three weeks, or once every four weeks.
29. Cancers include colorectal cancer (CRC), gastric cancer, esophageal cancer, cervical cancer, bladder cancer, breast cancer, head and neck cancer, ovarian cancer, melanoma, renal cell cancer (RCC), EC squamous cell carcinoma, non-small cell lung cancer , The anti-ICOS antibody and anti-PD1 antibody according to any one of 19 and 21-28, or any of 20-29 above, selected from the group consisting of mesopharyngeal carcinoma, pancreatic cancer, and prostate cancer. Anti-ICOS antibody and anti-PD-L1 antibody.
30. Use of an anti-ICOS antibody or its antigen-binding portion and an anti-PD1 antibody or its antigen-binding portion in the manufacture of a pharmaceutical for the treatment of cancer, the anti-ICOS antibody or its antigen-binding portion and the anti-PD1 antibody. Or the use described above, wherein the antigen-binding portion thereof is administered sequentially, and the anti-ICOS antibody or the antigen-binding portion thereof is administered followed by the anti-PD1 antibody or the antigen-binding portion thereof.
31. Use of an anti-ICOS antibody or its antigen-binding portion and an anti-PDL1 antibody or its antigen-binding portion in the manufacture of a pharmaceutical for the treatment of cancer, the anti-ICOS antibody or its antigen-binding portion and the anti-PDL1 antibody. Or the above-mentioned use, wherein the antigen-binding portion thereof is administered sequentially, and the anti-ICOS antibody or the antigen-binding portion thereof is administered followed by the anti-PDL1 antibody or the antigen-binding portion thereof.
32. A polynucleotide encoding an anti-ICOS antibody or antigen-binding portion thereof, wherein the anti-ICOS antibody or antigen-binding portion thereof is sequentially administered to a cancer patient together with an anti-PD1 antibody or antigen-binding portion thereof. And the above-mentioned polynucleotide to which the anti-PD1 antibody or the antigen-binding portion thereof is administered following the administration of the anti-ICOS antibody or the antigen-binding portion thereof.
33. A polynucleotide encoding an anti-ICOS antibody or antigen-binding portion thereof, wherein the anti-ICOS antibody or antigen-binding portion thereof is sequentially administered to a cancer patient together with an anti-PDL1 antibody or antigen-binding portion thereof. And the above-mentioned polynucleotide to which the anti-PDL1 antibody or the antigen-binding portion thereof is administered following the administration of the anti-ICOS antibody or the antigen-binding portion thereof.
34. A polynucleotide encoding an anti-PD1 antibody or antigen-binding portion thereof, wherein the anti-PD1 antibody or antigen-binding portion thereof is sequentially administered to a cancer patient together with an anti-ICOS antibody or antigen-binding portion thereof. And the above-mentioned polynucleotide to which the anti-PD1 antibody or the antigen-binding portion thereof is administered following the administration of the anti-ICOS antibody or the antigen-binding portion thereof.
35. A polynucleotide encoding an anti-PDL1 antibody or antigen-binding portion thereof, wherein the anti-PDL1 antibody or antigen-binding portion thereof is sequentially administered to a cancer patient together with an anti-ICOS antibody or antigen-binding portion thereof. And the above-mentioned polynucleotide to which the anti-PDL1 antibody or the antigen-binding portion thereof is administered following the administration of the anti-ICOS antibody or the antigen-binding portion thereof.
36. A vector containing the polynucleotide according to any one of 32 to 35 above.
37. A host cell containing the vector according to 36 above.
38. A method for producing an anti-ICOS antibody or an antigen-binding portion thereof.
(a) A step of culturing a host cell containing the polynucleotide according to 32 or 33 above under conditions suitable for expressing an anti-ICOS antibody or antigen-binding portion thereof; and
(b) The method described above comprising the step of isolating the anti-ICOS antibody or antigen-binding portion thereof.
39. A method for producing an anti-PD1 antibody or an antigen-binding portion thereof.
(a) A step of culturing a host cell containing the polynucleotide according to 34 above under conditions suitable for expressing an anti-PD1 antibody or an antigen-binding portion thereof; and
(b) The method described above comprising the step of isolating the anti-PD1 antibody or antigen-binding portion thereof.
40. A method for producing an anti-PDL1 antibody or an antigen-binding portion thereof.
(a) A step of culturing a host cell containing the polynucleotide according to 35 above under conditions suitable for expressing an anti-PDL1 antibody or an antigen-binding portion thereof; and
(b) The method described above comprising the step of isolating the anti-PDL1 antibody or antigen-binding portion thereof.

Claims (14)

それを必要とするヒトでの癌の治療での逐次的使用のための、抗ICOS抗体またはその抗原結合性断片、および抗PD1抗体またはその抗原結合性断片であって、抗ICOS抗体またはその抗原結合性断片の投与に続いて、抗PD1抗体またはその抗原結合性断片が投与される、上記抗体またはその抗原結合性断片。 Anti-ICOS antibody or antigen-binding fragment thereof, and anti-PD1 antibody or antigen-binding fragment thereof for sequential use in the treatment of cancer in humans who require it, and anti-ICOS antibody or antigen thereof. The antibody or antigen-binding fragment thereof , wherein the anti-PD1 antibody or antigen-binding fragment thereof is administered following administration of the binding fragment. それを必要とするヒトでの癌の治療での逐次的使用のための、抗ICOS抗体またはその抗原結合性断片、および抗PD-L1抗体またはその抗原結合性断片であって、抗ICOS抗体またはその抗原結合性断片の投与に続いて、抗PD-L1抗体またはその抗原結合性断片が投与される、上記抗体またはその抗原結合性断片。 An anti-ICOS antibody or antigen-binding fragment thereof, and an anti-PD-L1 antibody or antigen-binding fragment thereof for sequential use in the treatment of cancer in humans in need thereof, the anti-ICOS antibody or The antibody or antigen-binding fragment thereof , to which an anti-PD-L1 antibody or antigen-binding fragment thereof is administered following administration of the antigen-binding fragment. PD-1アンタゴニストである、請求項1または2に記載の抗PD1抗体または抗PD-L1抗体。 The anti-PD1 antibody or anti-PD-L1 antibody according to claim 1 or 2 , which is a PD-1 antagonist. ペンブロリズマブまたはニボルマブである、請求項1または3に記載の抗PD1抗体。 The anti-PD1 antibody according to claim 1 or 3 , which is pembrolizumab or nivolumab. ICOSを標的とするアゴニスト抗体である、請求項1〜4のいずれか1項に記載の抗ICOS抗体。 The anti-ICOS antibody according to any one of claims 1 to 4 , which is an agonist antibody that targets ICOS. 配列番号7で表わされるアミノ酸配列に対して少なくとも90％同一なアミノ酸配列を含むVHドメイン、および配列番号8で表わされるアミノ酸配列に対して少なくとも90％同一なアミノ酸配列を含むVLドメインを含む、請求項1〜5のいずれか1項に記載の抗ICOS抗体。 Includes a V H domain containing an amino acid sequence that is at least 90% identical to the amino acid sequence represented by SEQ ID NO: 7 and a V L domain that contains an amino acid sequence that is at least 90% identical to the amino acid sequence represented by SEQ ID NO: 8. , The anti-ICOS antibody according to any one of claims 1 to 5. 配列番号7で表わされるアミノ酸配列を含むVHドメイン、および配列番号8で表わされるアミノ酸配列を含むVLドメインを含む、請求項1〜6のいずれか1項に記載の抗ICOS抗体。 The anti-ICOS antibody according to any one of claims 1 to 6 , comprising a V H domain containing the amino acid sequence represented by SEQ ID NO: 7 and a VL domain containing the amino acid sequence represented by SEQ ID NO: 8. 週1回、2週間に1回、3週間に1回、または4週間に1回投与される、請求項1〜7のいずれか1項に記載の抗ICOS抗体またはその抗原結合性断片。 The anti-ICOS antibody or antigen-binding fragment thereof according to any one of claims 1 to 7 , which is administered once a week, once every two weeks, once every three weeks, or once every four weeks. 週1回、2週間に1回、3週間に1回、または4週間に1回投与される、請求項1〜8のいずれか1項に記載の抗PD1抗体もしくはその抗原結合性断片または抗PD-L1抗体もしくはその抗原結合性断片。 The anti-PD1 antibody or antigen-binding fragment thereof or anti-PD1 antibody according to any one of claims 1 to 8 , which is administered once a week, once every two weeks, once every three weeks, or once every four weeks. PD-L1 antibody or antigen-binding fragment thereof . 癌が、結腸直腸癌（CRC）、胃癌、食道癌、子宮頸癌、膀胱癌、乳癌、頭頚部癌、卵巣癌、黒色腫、腎細胞癌（RCC）、EC扁平上皮癌、非小細胞肺癌、中皮腫、膵臓癌、および前立腺癌からなる群より選択される、請求項1および3〜9のいずれか1項に記載の抗ICOS抗体もしくはその抗原結合性断片および抗PD1抗体もしくはその抗原結合性断片、または請求項2および6〜9のいずれか1項に記載の抗ICOS抗体もしくはその抗原結合性断片および抗PD-L1抗体もしくはその抗原結合性断片。 Cancers include colorectal cancer (CRC), gastric cancer, esophageal cancer, cervical cancer, bladder cancer, breast cancer, head and neck cancer, ovarian cancer, melanoma, renal cell cancer (RCC), EC squamous cell carcinoma, non-small cell lung cancer The anti-ICOS antibody according to any one of claims 1 and 3 to 9 , and an antigen-binding fragment thereof and an anti-PD1 antibody or an antigen thereof , selected from the group consisting of mesopharyngeal carcinoma, pancreatic cancer, and prostate cancer. The binding fragment , or the anti-ICOS antibody or antigen-binding fragment thereof according to any one of claims 2 and 6 to 9 , and the anti-PD-L1 antibody or antigen-binding fragment thereof . 抗PD1抗体もしくはその抗原結合性部分、または抗PD-L1抗体もしくはその抗原結合性部分が、抗ICOS抗体もしくはその抗原結合性部分の投与開始の1週間後、2週間後、3週間後、および4週間後から選択される時点で投与される、請求項1および3〜10のいずれか1項に記載の抗ICOS抗体もしくはその抗原結合性断片および抗PD1抗体もしくはその抗原結合性断片、または請求項2および6〜10のいずれか1項に記載の抗ICOS抗体もしくはその抗原結合性断片および抗PD-L1抗体もしくはその抗原結合性断片。The anti-PD1 antibody or its antigen-binding portion, or the anti-PD-L1 antibody or its antigen-binding portion, 1 week, 2 weeks, 3 weeks, and after the start of administration of the anti-ICOS antibody or its antigen-binding portion. The anti-ICOS antibody or antigen-binding fragment thereof and the anti-PD1 antibody or antigen-binding fragment thereof, which is administered at a time selected from 4 weeks later, according to any one of claims 1 and 3 to 10. Item 2. The anti-ICOS antibody or an antigen-binding fragment thereof according to any one of Items 2 and 6 to 10, and an anti-PD-L1 antibody or an antigen-binding fragment thereof. 抗ICOS抗体もしくはその抗原結合性部分、および抗PD1抗体もしくはその抗原結合性部分、または抗PD-L1抗体もしくはその抗原結合性部分が、疾患進行または許容不能な毒性が示されるまで投与される、請求項1および3〜11のいずれか1項に記載の抗ICOS抗体もしくはその抗原結合性断片および抗PD1抗体もしくはその抗原結合性断片、または請求項2および6〜11のいずれか1項に記載の抗ICOS抗体もしくはその抗原結合性断片および抗PD-L1抗体もしくはその抗原結合性断片。The anti-ICOS antibody or its antigen-binding portion, and the anti-PD1 antibody or its antigen-binding portion, or the anti-PD-L1 antibody or its antigen-binding portion are administered until disease progression or unacceptable toxicity. The anti-ICOS antibody or the antigen-binding fragment thereof according to any one of claims 1 and 3 to 11 and the anti-PD1 antibody or the antigen-binding fragment thereof, or any one of claims 2 and 6 to 11. Anti-ICOS antibody or antigen-binding fragment thereof and anti-PD-L1 antibody or antigen-binding fragment thereof. 癌の治療のための医薬の製造での、抗ICOS抗体またはその抗原結合性部分および抗PD1抗体またはその抗原結合性部分の使用であって、抗ICOS抗体またはその抗原結合性部分および抗PD1抗体またはその抗原結合性部分が逐次的に投与され、かつ抗ICOS抗体またはその抗原結合性部分の投与に続いて抗PD1抗体またはその抗原結合性部分が投与される、上記使用。 Use of an anti-ICOS antibody or its antigen-binding portion and an anti-PD1 antibody or its antigen-binding portion in the manufacture of a pharmaceutical for the treatment of cancer, the anti-ICOS antibody or its antigen-binding portion and the anti-PD1 antibody. Or the use described above, wherein the antigen-binding portion thereof is administered sequentially, and the anti-ICOS antibody or the antigen-binding portion thereof is administered followed by the anti-PD1 antibody or the antigen-binding portion thereof. 癌の治療のための医薬の製造での、抗ICOS抗体またはその抗原結合性部分および抗PD-L1抗体またはその抗原結合性部分の使用であって、抗ICOS抗体またはその抗原結合性部分および抗PD-L1抗体またはその抗原結合性部分が逐次的に投与され、かつ抗ICOS抗体またはその抗原結合性部分の投与に続いて抗PD-L1抗体またはその抗原結合性部分が投与される、上記使用。 Use of an anti-ICOS antibody or its antigen-binding portion and an anti- PD-L1 antibody or its antigen-binding portion in the manufacture of a pharmaceutical for the treatment of cancer, the anti-ICOS antibody or its antigen-binding portion and anti. PD-L1 antibody or antigen-binding portion thereof is sequentially administered, and anti-ICOS antibody or antigen-binding portion thereof is administered followed by anti- PD-L1 antibody or antigen-binding portion thereof, the above-mentioned use. ..
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