JPWO2021087016A5 - - Google Patents

Claims (37)

A pharmaceutical composition comprising from about 2 mg to about 700 mg of an anti-CD27 antibody or antigen-binding fragment thereof comprising a heavy chain and a light chain for the treatment of cancer in a patient, the composition comprising:
wherein the light chain comprises light chain CDRs comprising the amino acid sequences of SEQ ID NOs: 4, 5 and 6, respectively, and the heavy chain comprises heavy chain CDRs comprising the amino acid sequences of SEQ ID NOs: 1, 2 and 3, respectively. , said pharmaceutical composition. 2. The pharmaceutical composition of claim 1, wherein the anti-CD27 antibody or antigen-binding fragment thereof is administered by intravenous infusion. 3. The pharmaceutical composition of claim 1 or 2, wherein 2 mg, 7 mg, 20 mg, 30 mg, 70 mg or 700 mg of anti-CD27 antibody or antigen-binding fragment thereof is administered to the patient. 2. The pharmaceutical composition of claim 1, wherein the anti-CD27 antibody or antigen-binding fragment thereof is administered to the patient at a dose of about 30 mg, about 200 mg, or about 200 mg to about 700 mg. The pharmaceutical composition of any one of claims 1-4, wherein the anti-CD27 antibody or antigen-binding fragment thereof is administered to the patient at least once on day 1 and then about 3 weeks to about 6 weeks later. thing. The anti-CD27 antibody or antigen-binding fragment thereof comprises a heavy chain and a light chain, and wherein the heavy chain comprises a heavy chain variable region comprising SEQ ID NO: 7 and the light chain comprises a light chain comprising SEQ ID NO: 9. A pharmaceutical composition according to any one of claims 1 to 5, comprising a chain variable region. 8. The anti-CD27 antibody or antigen-binding fragment thereof comprises a heavy chain and a light chain, and wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 8 and the light chain comprises the amino acid sequence of SEQ ID NO: 10. 7. The pharmaceutical composition according to any one of 1 to 6. The pharmaceutical composition according to any one of claims 1 to 5, wherein the anti-CD27 antibody or antigen-binding fragment thereof is an anti-CD27 antibody. The pharmaceutical composition according to any one of claims 1 to 8, wherein the anti-CD27 antibody or antigen-binding fragment thereof is co-administered with an anti-PD-1 antibody or anti-PD-L1 antibody or antigen-binding fragment thereof. A pharmaceutical composition according to any one of claims 1 to 8, wherein the anti-CD27 antibody is co-formulated with an anti-PD-1 antibody or an anti-PD-L1 antibody or an antigen-binding fragment thereof. The pharmaceutical composition according to claim 9 or 10, wherein the anti-PD-1 antibody or antigen-binding fragment thereof specifically binds to human PD-1 and blocks binding of human PD-L1 to human PD-1. . 12. The pharmaceutical composition of claim 11, wherein the anti-PD-1 antibody or antigen-binding fragment thereof also blocks binding of human PD-L2 to human PD-1. 12. The anti-PD-1 antibody or antigen-binding fragment thereof comprises (a) light chain CDRs of SEQ ID NOs: 11, 12 and 13, and (b) heavy chain CDRs of SEQ ID NOs: 16, 17 and 18. Pharmaceutical compositions as described. The anti-PD-1 antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 19, and the light chain comprises the amino acid sequence of SEQ ID NO: 14. 14. The pharmaceutical composition of claim 13, comprising a light chain variable region comprising: 15. The medicament of claim 14, wherein the anti-PD-1 antibody comprises a heavy chain and a light chain, and wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 20 and the light chain comprises the amino acid sequence of SEQ ID NO: 15. Composition. The pharmaceutical composition according to claim 9 or 10, wherein the anti-PD-1 antibody is pembrolizumab, a pembrolizumab variant, or nivolumab, or the anti-PD-L1 antibody is atezolizumab, durvalumab, or avelumab. The pharmaceutical composition according to any one of claims 1 to 16, wherein the anti-CD27 antibody or antigen-binding fragment thereof is administered every three weeks (Q3W) or every six weeks (Q6W). thing. Anti-PD-1 antibody is
(i) 200 mg by intravenous infusion on day 1 and every 3 weeks thereafter, or (ii) 400 mg by intravenous infusion on day 1 and then every 6 weeks thereafter. administered twice,
The pharmaceutical composition according to any one of claims 9 to 17. The anti-PD-1 antibody is a humanized anti-PD-1 antibody comprising a heavy chain and a light chain, and wherein the heavy chain comprises a heavy chain variable region comprising the heavy chain CDRs of SEQ ID NO: 16, 17 and 18, respectively. and the light chain comprises a light chain variable region comprising light chain CDRs comprising the amino acid sequences of SEQ ID NOs: 11, 12 and 13, respectively, and the anti-CD27 antibody is a humanized humanized antibody comprising a heavy chain and a light chain. an anti-CD27 antibody, and wherein the heavy chain comprises a heavy chain variable region comprising heavy chain CDRs comprising the amino acid sequences of SEQ ID NO: 1, 2 and 3, respectively, and the light chain comprises a heavy chain CDR comprising the amino acid sequences of SEQ ID NO: 4, SEQ ID NO: 4, respectively. 11. The pharmaceutical composition according to claim 9 or 10, comprising a light chain variable region comprising light chain CDRs comprising amino acid sequences of 5 and 6. The anti-PD-1 antibody comprises a heavy chain and a light chain, where the heavy chain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 19, and the light chain comprises the amino acid sequence of SEQ ID NO: 14. and the anti-CD27 antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7, and the light chain comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7; 11. The pharmaceutical composition according to claim 9 or 10, comprising a light chain variable region comprising the amino acid sequence of SEQ ID NO: 9. The anti-PD-1 antibody comprises a heavy chain and a light chain, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 20, and the light chain comprises the amino acid sequence of SEQ ID NO: 15, and the anti-CD27 antibody comprises 11. The pharmaceutical composition of claim 9 or 10, comprising a heavy chain and a light chain, and wherein the heavy chain comprises the amino acid sequence of SEQ ID NO: 8 and the light chain comprises the amino acid sequence of SEQ ID NO: 10. Anti-PD-1 antibody is
a. 200 mg by intravenous infusion on day 1 and once every 3 weeks thereafter; administered, or
b. 400 mg by intravenous infusion on day 1 and once every 6 weeks thereafter; administered,
The pharmaceutical composition according to any one of claims 9, 10 or 19-21. A pharmaceutical composition according to any one of claims 19 to 22, wherein the anti-PD-1 antibody is co-formulated with an anti-CD27 antibody. A pharmaceutical composition according to any one of claims 1 to 21, wherein the cancer comprises a solid tumor. The cancer is selected from the group consisting of triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), small cell lung cancer and endometrial cancer, and optionally the NSCLC is non-squamous non-small cell lung cancer. 23. The pharmaceutical composition according to any one of items 1 to 22. Pharmaceutical composition according to any one of claims 1 to 25, wherein the pharmaceutical composition is administered in combination with carboplatin and/or pemetrexed. The patient has not been previously treated with anti-PD-1 or anti-PD-L1 therapy or has been confirmed to be progressive while receiving previous anti-PD-1 or anti-PD-L1 therapy , the pharmaceutical composition according to any one of claims 1 to 25. Pharmaceutical composition according to any one of claims 1 to 25, wherein the patient is administered an analgesic and/or an antihistamine before the anti-CD27 antibody or antigen-binding fragment thereof. Use of an anti-CD27 antibody or an antigen-binding fragment thereof according to any one of claims 1 to 8 in the preparation of a medicament for the treatment of cancer. 30. The use according to claim 29, wherein the anti-CD27 antibody or antigen binding fragment is combined with a pharmaceutically acceptable carrier or diluent. 31. Use according to claim 29 or 30, further comprising at least one therapeutic substance. 32. The use according to claim 31, wherein said at least one therapeutic substance is an anti-PD-1 antibody or an anti-PD-L1 antibody or an antigen-binding fragment thereof according to any one of the preceding claims. 33. The use according to claim 32, wherein the anti-CD27 antibody or antigen-binding fragment thereof is co-administered with an anti-PD-1 antibody or anti-PD-L1 antibody or antigen-binding fragment thereof. A pharmaceutical composition comprising about 2 mg to about 700 mg of an anti-CD27 antibody or antigen-binding fragment thereof and a pharmaceutically acceptable excipient, the composition comprising:
Here, the antibody or antigen-binding fragment thereof includes a heavy chain and a light chain,
wherein the light chain comprises light chain CDRs comprising the amino acid sequences of SEQ ID NOs: 4, 5 and 6, respectively, and the heavy chain comprises heavy chain CDRs comprising the amino acid sequences of SEQ ID NOs: 1, 2 and 3, respectively. , said pharmaceutical composition. A kit comprising about 2 mg to about 700 mg of an anti-CD27 antibody or antigen-binding fragment thereof and instructions for use, the kit comprising:
Here, the antibody or antigen-binding fragment thereof includes a heavy chain and a light chain,
wherein the light chain comprises light chain CDRs comprising the amino acid sequences of SEQ ID NOs: 4, 5 and 6, respectively, and the heavy chain comprises heavy chain CDRs comprising the amino acid sequences of SEQ ID NOs: 1, 2 and 3, respectively. , said kit. 35. A pharmaceutical composition according to claim 1 or 34, wherein the anti-CD27 antibody or antigen-binding fragment is expressed by CHO cells. 35. The pharmaceutical composition of claim 1 or 34, wherein the anti-CD27 antibody or antigen-binding fragment comprises a glycosylation pattern characteristic of expression by CHO cells.