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US-12617850-B2 - Treatment of PD-L1-positive melanoma using an anti-PD-1 antibody

US12617850B2US 12617850 B2US12617850 B2US 12617850B2US-12617850-B2

Abstract

The invention provides a method of treating a melanoma comprising (i) identifying a patient having a PD-L1 positive melanoma and (ii) administering to the patient an anti-PD-1 antibody or an antigen-binding portion thereof (“an anti-PD-1 antibody monotherapy”). The methods of the invention can extend progression-free survival for over 12 months and/or reduces the tumor size at least about 10%, about 20%, about 30%, about 40%, or about 50% compared to the tumor size prior to the administration.

Inventors

  • Arvin YANG

Assignees

  • BRISTOL-MYERS SQUIBB COMPANY

Dates

Publication Date
20260505
Application Date
20220322

Claims (10)

  1. 1 . A method for treating a melanoma tumor in a patient in need thereof comprising: (i) identifying a patient having a PD-L1 positive melanoma tumor, wherein the PD-L1 positive melanoma tumor is characterized by at least about 5% of tumor cells expressing PD-L1 in a test tissue sample obtained from the patient, the test tissue sample comprising tumor cells and/or tumor-infiltrating inflammatory cells; and (ii) administering to the patient a flat dose of 480 mg of nivolumab or an antigen-binding portion thereof that binds specifically to a human PD-1 once every four weeks, without regard for the weight or body surface area (BSA) of the patient, wherein the patient is not administered a combination of nivolumab or an antigen-binding portion thereof and another anti-cancer agent.
  2. 2 . The method of claim 1 , wherein the patient is characterized by (i) extended progression-free survival for over 12 months following the administration, (ii) tumor size reduction at least about 10% compared to the tumor size prior to the administration, or (iii) both (i) and (ii).
  3. 3 . The method of claim 1 , wherein the test tissue sample is a formalin-fixed paraffin-embedded (FFPE) tissue sample.
  4. 4 . The method of claim 1 , wherein the expression of PD-L1 is determined using an automated IHC assay.
  5. 5 . The method of claim 4 , wherein the IHC assay is performed using an anti-PD-L1 monoclonal antibody that specifically binds to the PD-L1 and wherein the anti-PD-L1 monoclonal antibody comprises a heavy chain CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 3, a heavy chain CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 4, a heavy chain CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 5, a light chain CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 6, a light chain CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8.
  6. 6 . A method for treating a melanoma tumor in a patient in need thereof comprising administering to the patient a flat dose of 480 mg of nivolumab or an antigen-binding portion thereof that binds specifically to a human PD-1 once every four weeks, without regard for the weight or body surface area (BSA) of the patient, wherein the patient is not administered a combination of nivolumab or an antigen-binding portion thereof and another anti-cancer agent, wherein the patient is identified as having a PD-L1 positive melanoma tumor prior to the administration, wherein the PD-L1 positive melanoma tumor is characterized by at least about 5% of tumor cells expressing PD-L1 in a test tissue sample obtained from the patient, the test tissue sample comprising tumor cells and/or tumor-infiltrating inflammatory cells.
  7. 7 . The method of claim 6 , wherein the patient is characterized by (i) extended progression-free survival for over 12 months following the administration, (ii) tumor size reduction at least about 10% compared to the tumor size prior to the administration, or (iii) both (i) and (ii).
  8. 8 . The method of claim 6 , wherein the test tissue sample is a formalin-fixed paraffin-embedded (FFPE) tissue sample.
  9. 9 . The method of claim 8 , wherein the expression of PD-L1 is determined using an automated IHC assay.
  10. 10 . The method of claim 9 , wherein the IHC assay is performed using an anti-PD-L1 monoclonal antibody that specifically binds to the PD-L1 and wherein the anti-PD-L1 monoclonal antibody comprises a heavy chain CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 3, a heavy chain CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 4, a heavy chain CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 5, a light chain CDR1 comprising the amino acid sequence set forth in SEQ ID NO: 6, a light chain CDR2 comprising the amino acid sequence set forth in SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence set forth in SEQ ID NO: 8.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS The present application is a continuation of U.S. application Ser. No. 16/430,106 filed on Jun. 3, 2019, which is a continuation of U.S. application Ser. No. 15/141,772 filed Apr. 28, 2016, which claims benefit to U.S. Provisional Application No. 62/153,954 filed Apr. 28, 2015, each of which is incorporated herein by reference in its entirety. REFERENCE TO A SEQUENCE LISTING SUBMITTED ELECTRONICALLY VIA EFS-WEB The instant application contains a Sequence Listing which has been submitted in ASCII format via EFS-Web, and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Mar. 22, 2022, is named 3338_0320004_Seqlisting_ST25.txt and is 3,785 bytes in size. Throughout this application, various publications are referenced in parentheses by author name and date, or by patent No. or patent Publication No. The disclosures of these publications are hereby incorporated in their entireties by reference into this application in order to more fully describe the state of the art as known to those skilled therein as of the date of the invention described and claimed herein. However, the citation of a reference herein should not be construed as an acknowledgement that such reference is prior art to the present invention. FIELD OF THE INVENTION This invention relates to a method of treating PD-L1-positive melanoma comprising administering an anti-PD-1 antibody. BACKGROUND OF THE INVENTION Human cancers harbor numerous genetic and epigenetic alterations, generating neoantigens potentially recognizable by the immune system (Sjoblom et al. (2006) Science 314:268-74). The adaptive immune system, comprised of T and B lymphocytes, has powerful anti-cancer potential, with a broad capacity and exquisite specificity to respond to diverse tumor antigens. Further, the immune system demonstrates considerable plasticity and a memory component. The successful harnessing of all these attributes of the adaptive immune system would make immunotherapy unique among all cancer treatment modalities. Recently, several immune checkpoint pathway inhibitors have begun to provide new immunotherapeutic approaches for treating cancer, including the development of an antibody (Ab), ipilimumab (YERVOY®), that binds to and inhibits Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) for the treatment of patients with advanced melanoma and the development of antibodies such as nivolumab and pembrolizumab (formerly lambrolizumab; USAN Council Statement, (2013) Pembrolizumab: Statement on a nonproprietary name adopted by the USAN Council (ZZ-165), Nov. 27, 2013) that bind specifically to the Programmed Death-1 (PD-1) receptor and block the inhibitory PD-1/PD-1 ligand pathway. The promise of the emerging field of personalized medicine is that advances in pharmacogenomics will increasingly be used to tailor therapeutics to defined sub-populations, and ultimately, individual patients in order to enhance efficacy and minimize adverse effects. Recent successes include, for example, the development of imatinib mesylate (GLEEVEC®), a protein tyrosine kinase inhibitor that inhibits the bcr-abl tyrosine kinase, to treat Philadelphia chromosome-positive chronic myelogenous leukemia (CML); crizotinib (XALKORI®) to treat the 5% of patients with late-stage non-small cell lung cancers who express a mutant anaplastic lymphoma kinase (ALK) gene; and vemurafenib (ZELBORAF®), an inhibitor of mutated B-RAF protein (V600E-BRAF) which is expressed in around half of melanoma tumors. However, unlike the clinical development of small molecule agents that target discrete activating mutations found in select cancer populations, a particular challenge in cancer immunotherapy has been the identification of mechanism-based predictive biomarkers to enable patient selection and guide on-treatment management. SUMMARY OF THE INVENTION The present disclosure provides a method for treating a melanoma comprising (i) identifying a patient having a PD-L1 positive melanoma tumor; and (ii) administering to the patient an anti-PD-1 antibody or an antigen-binding portion thereof that binds specifically to a human PD-1 (“anti-PD1 antibody monotherapy”), wherein the patient is not administered a combination of an anti-PD-1 antibody or an antigen-binding portion thereof and an anti-CTLA-4 antibody or an antigen-binding portion thereof that binds specifically to a human CTLA-4 (“combination therapy”). The present disclosure also provides a method for treating a melanoma comprising (i) identifying a patient having a PD-L1 positive melanoma tumor; (ii) administering to the patient an anti-PD-1 antibody monotherapy; and (iii) administering a combination therapy to the patient, wherein the patient does not show efficacy with the anti-PD-1 monotherapy. The present disclosure further provides a method for treating a melanoma comprising administering to a patient afflicted with a melanoma tumor an anti-PD-1 antibody monotherapy, not a combination ther