IP Library › Granted Patent US 12,473,364
Granted Patent B2
US 12,473,364 · App. 17/292,179 · Granted Nov 18, 2025

Intralesional administration of PD-1 inhibitors for treating skin cancer

Inventors: Matthew G. Fury (New York, NY); Israel Lowy (Dobbs Ferry, NY)
Assignee: Regeneron Pharmaceuticals, Inc.
C07K16/2827A61K9/0019A61K9/08C07K16/2818C07K2317/51C07K2317/515C07K2317/56C07K2317/565
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Quick Facts
Patent No.
US 12,473,364
App. No.
17/292,179
Granted
Nov 18, 2025
Kind
B2
Abstract

The disclosure relates to methods for treating or inhibiting the growth of a tumor, wherein the methods include selecting a subject with a skin cancer and intralesionally administering to the tumor of the subject in need thereof a therapeutically effective amount of a programmed death 1 (PD-1) inhibitor (e.g., an antibody or antigen-binding fragment thereof that specifically binds PD-1, PD-L1, and/or PD-L2). In certain embodiments, the skin cancer is cutaneous squamous cell carcinoma. In certain embodiments, the PD-1 inhibitor is administered into multiple locations of the tumor lesion.

Claims (33)

1 . A method of treating or inhibiting the growth of a tumor, comprising:

(a) selecting a patient with a skin cancer; and

(b) intralesionally administering to the tumor of the patient one or more doses of a pharmaceutical composition comprising a therapeutically effective amount of a programmed death 1 (PD-1) inhibitor, wherein the PD-1 inhibitor is an antibody or antigen-binding fragment thereof that specifically binds PD-1 and comprises three complementarity determining regions (CDRs) (HCDR1, HCDR2, and HCDR3) of a heavy chain variable region (HCVR) comprising the amino acid sequence of SEQ ID NO: 1 and three CDRs (LCDR1, LCDR2, and LCDR3) of a light chain variable region (LCVR) comprising the amino acid sequence of SEQ ID NO: 2 wherein the skin cancer is cutaneous squamous cell carcinoma (CSCC) or basal cell carcinoma (BCC).

2 . The method according to claim 1 , wherein the skin cancer is CSCC.

3 . The method according to claim 1 , wherein the skin cancer is recurrent resectable CSCC.

4 . The method according to claim 1 , wherein the patient has had prior treatment for the cancer.

5 . The method according to claim 4 , wherein the prior treatment comprises surgery, radiation, chemotherapy, treatment with a PD-1 inhibitor, and/or other anti-tumor therapy.

6 . The method according to claim 1 , wherein the patient is at risk of recurrence.

7 . The method according to claim 1 , wherein the patient has a prior history of recurrence after surgery.

8 . The method according to claim 1 , wherein each dose of the PD-1 inhibitor comprises one or more intralesional injections of the pharmaceutical composition into the tumor.

9 . The method according to claim 8 , wherein at least two intralesional injections are administered into different locations of the tumor.

10 . The method according to claim 8 , wherein two to five intralesional injections are administered into two to five locations of the tumor.

11 . The method according to claim 8 , wherein at least one intralesional injection is administered into the upper half of the tumor.

12 . The method according to claim 8 , wherein at least one intralesional injection is administered into skin overlying the tumor.

13 . The method according to claim 8 , wherein at least one intralesional injection is administered into a superior periphery of the tumor, adjacent an interface with normal-appearing skin.

14 . The method according to claim 1 , wherein the tumor has a surface diameter of at least 1 cm.

15 . The method according to claim 1 , wherein the tumor has a surface diameter of no more than 2 cm.

16 . The method according to claim 1 , wherein each dose is administered once a day, once in two days, once in three days, once in four days, once in five days, once in six days, once a week or twice a week.

17 . The method according to claim 1 , wherein each dose comprises 5 mg to 200 mg of the PD-1 inhibitor.

18 . The method according to claim 1 , wherein each dose comprises 5 mg, 15 mg, or 44 mg of the PD-1 inhibitor.

19 . The method according to claim 1 , wherein the administration of the PD-1 inhibitor promotes tumor regression, reduces tumor cell load, reduces tumor burden, and/or prevents tumor recurrence in the patient.

20 . The method according to claim 1 , wherein the intralesional administration of the PD-1 inhibitor promotes at least about 10% more tumor regression than intravenous administration of the PD-1 inhibitor.

21 . The method according to claim 1 , wherein the intralesional administration of the PD-1 inhibitor leads to lower incidence of adverse events, less severity of adverse events, and/or less toxicity than intravenous administration of the PD-1 inhibitor.

22 . The method according to claim 1 , further comprising surgically removing the tumor after step (b).

23 . The method according to claim 1 , further comprising administering a second therapeutic agent or therapy selected from surgery, radiation, chemotherapy, a corticosteroid, an anti-inflammatory drug, and/or combinations thereof.

24 . The method of claim 23 , wherein the PD-1 inhibitor is administered before a second therapeutic agent or therapy.

25 . The method of claim 23 , wherein the PD-1 inhibitor is administered after a second therapeutic agent or therapy.

26 . The method according to claim 1 , wherein: HCDR1 has an amino acid sequence of SEQ ID NO: 3; HCDR2 has an amino acid sequence of SEQ ID NO: 4; HCDR3 has an amino acid sequence of SEQ ID NO: 5; LCDR1 has an amino acid sequence of SEQ ID NO: 6; LCDR2 has an amino acid sequence of SEQ ID NO: 7; and LCDR3 has an amino acid sequence of SEQ ID NO: 8.

27 . The method according to claim 26 , wherein the anti-PD-1 antibody or antigen-binding fragment thereof comprises a HCVR/LCVR sequence pair of SEQ ID NOs: 1/2.

28 . The method according to claim 27 , wherein the anti-PD-1 antibody comprises a heavy chain and a light chain, wherein the heavy chain has an amino acid sequence of SEQ ID NO: 9.

29 . The method according to claim 27 , wherein the anti-PD-1 antibody comprises a heavy chain and a light chain, wherein the light chain has an amino acid sequence of SEQ ID NO: 10.

30 . The method according to claim 27 , wherein the anti-PD-1 antibody comprises a heavy chain and a light chain, wherein the heavy chain has an amino acid sequence of SEQ ID NO: 9 and the light chain has an amino acid sequence of SEQ ID NO: 10.

31 . The method according to claim 1 , wherein the PD-1 inhibitor is cemiplimab or a bioequivalent thereof.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 20, 2024
From: FURY, MATTHEW G.; LOWY, ISRAEL
To: REGENERON PHARMACEUTICALS, INC.
Reel/Frame 067788/0810 →
Continuity (2)
Provisional Application 62767218 · Nov 14, 2018
Related Publication 20210388091A1 · Dec 16, 2021
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