NZ748192B2

NZ748192B2 - Methods of treating skin cancer by administering a pd-1 inhibitor

Info

Publication number: NZ748192B2
Application number: NZ748192A
Authority: NZ
Inventors: Matthew G Fury; Israel Lowy; Tasha N Sims
Original assignee: Regeneron Pharmaceuticals Inc
Filing date: 2017-05-12
Publication date: 2024-06-25

Abstract

The present disclosure provides methods for treating, reducing the severity, or inhibiting the growth of cutaneous squamous cell carcinoma. The methods of the present disclosure comprise administering to a subject in need thereof a therapeutically effective amount of a programmed death 1 (PD-1) antibody (e.g., Cemiplimab).

Claims

What is claimed is:

1. Use of an isolated antibody or antigen-binding fragment thereof that specifically binds programmed death 1 (PD-1) in the manufacture of a medicament for treating or inhibiting the growth of a tumor in a patient, wherein the tumor comprises cutaneous squamous cell carcinoma (CSCC), and wherein the D-1 antibody or antigen-binding fragment thereof comprises three heavy chain complementarity determining regions (HCDR1, HCDR2 and HCDR3) of a heavy chain variable region (HCVR) and three light chain complementarity determining regions (LCDR1, LCDR2 and LCDR3) of a light chain variable region (LCVR), wherein HCDR1 comprises the amino acid sequence of SEQ ID NO: 3; HCDR2 comprises the amino acid sequence of SEQ ID NO: 4; HCDR3 comprises the amino acid sequence of SEQ ID NO: 5; LCDR1 comprises the amino acid sequence of SEQ ID NO: 6; LCDR2 ses the amino acid sequence of SEQ ID NO: 7; and LCDR3 ses the amino acid sequence of SEQ ID NO: 8.

2. The use of claim 1, wherein the CSCC is metastatic, unresectable and/or locally advanced.

3. The use of any one of claims 1 – 2, wherein the CSCC is metastatic, and wherein said patient has been treated with at least one prior anti-cancer therapy selected from the group consisting of surgery, radiation, chemotherapy, and another anti-PD-1 antibody.

4. The use of any one of claims 1 – 3, n the patient is intolerant to or the CSCC progresses after prior treatment with an anti-cancer y.

5. The use of any one of claims 1 – 4, wherein the CSCC is locally advanced, and wherein said patient is not amenable to curative surgery.

6. The use of any one of claims 1 – 5, wherein said medicament is formulated to deliver said antibody or antigen-binding fragment thereof in one or more doses, and each dose is to be stered 0.5 to 4 weeks after the immediately preceding dose.

7. The use of claim 6, wherein said medicament is formulated such that each dose is to be administered 2 weeks after the immediately preceding dose.

8. The use of claim 6, wherein said ment is formulated so that each dose is to be administered 3 weeks after the immediately preceding dose.

9. The use of any one of claims 6 – 8, wherein each dose comprises 1, 3, or 10 mg/kg of patient’s body weight. 20630372_1 ters) P44583NZ00

10. The use of claim 9, wherein each dose comprises 3 mg/kg of the patient’s body weight.

11. The use of any one of claims 6 – 8, wherein each dose comprises 50 – 600 mg of the anti-PD-1 antibody or antigen-binding fragment thereof.

12. The use of claim 11, wherein each dose comprises 200, 250, or 350 mg of the anti-PD-1 antibody or antigen-binding fragment f.

13. The use of any one of claims 1 – 12, wherein the patient is resistant or inadequately responsive to, or relapsed after prior therapy.

14. The use of any one of claims 1 – 13, wherein the medicament is formulated for administration as a monotherapy.

15. The use of any one of claims 1 – 14, n said treating or inhibiting leads to at least one effect selected from the group consisting of inhibition of tumor growth, tumor regression, reduction in the size of a tumor, reduction in tumor cell number, delay in tumor growth, abscopal effect, inhibition of tumor metastasis, reduction in metastatic lesions over time, reduced use of chemotherapeutic or cytotoxic agents, reduction in tumor , increase in progression-free survival, increase in overall survival, complete response, partial response, and stable disease.

16. The use of any one of claims 1 – 13 and 15, wherein the anti-PD-1 antibody or antigen-binding fragment thereof is formulated for administration to the patient with a further additional therapeutic agent or therapy, n the additional therapeutic agent or therapy is selected from the group consisting of y, radiation, a chemotherapeutic agent, a cancer vaccine, a programmed death ligand 1 (PD-L1) inhibitor, a cyte activation gene 3 (LAG3) inhibitor, a cytotoxic T -lymphocyte-associated protein 4 (CTLA-4) inhibitor, a glucocorticoid-induced tumor is factor receptor (GITR) agonist, a T -cell globulin and mucin-domain ning-3 (TIM3) inhibitor, a B - and T-lymphocyte attenuator (BTLA) inhibitor, a T cell immunoreceptor with Ig and ITIM domains (TIGIT) inhibitor, a CD47 inhibitor, an indoleamine-2,3-dioxygenase (IDO) inhibitor, a bispecific anti-CD3/anti-CD20 antibody, a vascular elial growth factor (VEGF) antagonist, an angiopoietin-2 (Ang2) inhibitor, a transforming growth factor beta (TGFß) inhibitor, a CD38 inhibitor, an epidermal growth factor receptor (EGFR) inhibitor, granulocyte-macrophage colony-stimulating factor (GM-CSF), cyclophosphamide, an antibody to a tumor-specific n, Bacillus te-Guerin vaccine, a xin, an interleukin 6 receptor (IL-6R) inhibitor, an interleukin 4 receptor (IL-4R) 20630372_1 ters) P44583NZ00 inhibitor, an IL-10 inhibitor, IL-2, IL-7, IL-21, IL-15, an antibody-drug conjugate, an flammatory drug, and a dietary supplement.

17. The use of any one of claims 1 – 16, wherein the D-1 antibody or antigenbinding fragment thereof is formulated for intravenous, subcutaneous, or intraperitoneal administration.

18. The use of any one of claims 1 – 17, wherein the HCVR comprises the amino acid sequence of SEQ ID NO: 1 and the LCVR comprises the amino acid sequence of SEQ ID NO: 2.

19. The use of any one of claims 1 – 17, wherein the anti-PD-1 antibody or antigenbinding fragment thereof comprises a HCVR with 90% sequence identity to SEQ ID NO: 1.

20. The use of any one of claims 1 – 17, wherein the anti-PD-1 antibody or antigenbinding fragment thereof comprises a LCVR with 90% sequence identity to SEQ ID NO: 2.

21. The use of any one of claims 1 – 17, wherein the anti-PD-1 antibody or antigenbinding fragment thereof comprises a HCVR with 90% sequence ty to SEQ ID NO: 1 and a LCVR with 90% sequence ty to SEQ ID NO: 2.

22. The use of any one of claims 1 – 18, wherein the anti-PD-1 antibody or antigenbinding fragment thereof comprises a heavy chain comprising the amino acid ce of SEQ ID NO: 9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

23. The use of any one of claims 1 – 22, wherein the tumor comprises atic CSCC or locally advanced CSCC, the subject is not a candidate for ve surgery or curative radiation, and the medicament is formulated for intravenous administration of said antibody or antigen-binding fragment thereof at a dose of 350 mg every three weeks. 20630372_1 (GHMatters) P44583NZ00 v_w®>> wgsmmwrc LOESF é» Aggy—ER: 0:0 WEE :0 032 cod 2 F239". SEE 37. Ewcbmwb 8568: mmEmva E >Uonnc< SEEQE 0U — a.) D e 0.0. 4—1 >" c 4" '43 OH 9) C u ._ to (DD + + 0.0. > > grewIC N N £ \