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KR-20260068060-A - Treatment of non-small cell lung cancer using sacituzumab govitecan and anti-PD-1 antibodies or their antigen-binding fragments

KR20260068060AKR 20260068060 AKR20260068060 AKR 20260068060AKR-20260068060-A

Abstract

The present disclosure relates to a method for treating treatment-naive metastatic NSCLC in a patient, comprising administering sacituzumab govitecan (SG) and an anti-PD-1 antibody or an antigen-binding fragment thereof.

Inventors

  • 메칸, 사빈, 파티마
  • 피페르디, 빌랄
  • 오토, 에이미, 엘리자베스

Assignees

  • 길리애드 사이언시즈, 인코포레이티드
  • 엠에스디 인터내셔널 비즈니스 게엠베하
  • 엠에스디 인터내셔날 게엠베하

Dates

Publication Date
20260513
Application Date
20240814
Priority Date
20230815

Claims (20)

  1. As a method for treating metastatic NSCLC in patients who have not received prior systemic therapy for metastatic non-small cell lung cancer (NSCLC), a. 10 mg/kg of an antibody-drug conjugate (ADC) comprising an anti-Trop-2 antibody or an antigen-binding fragment thereof as an intravenous infusion on days 1 and 8 of one or more 21-day treatment cycles—the anti-Trop-2 antibody or the antigen-binding fragment thereof comprises a light chain complementarity determining region (CDR) comprising an amino acid sequence as described in SEQ ID NOs 13, 14, and 15 and a heavy chain CDR comprising an amino acid sequence as described in SEQ ID NOs 16, 17, and 18, wherein the ADC has the chemical formula MAb-CL2A-SN-38, said chemical formula represented as follows: and b. Co-administering 200 mg of an anti-PD-1 antibody or its antigen-binding fragment as an intravenous infusion on Day 1 of one or more 21-day treatment cycles, and The anti-PD-1 antibody or its antigen-binding fragment comprises a light chain CDR having an amino acid sequence as described in SEQ ID NOs. 3, 4, and 5 and a heavy chain CDR having an amino acid sequence as described in SEQ ID NOs. 8, 9, and 10, and the method achieves a complete or partial response in a patient.
  2. In claim 1, the method wherein the anti-Trop-2 antibody is sacituzumab.
  3. A method according to claim 1 or 2, wherein the ADC is sacituzumab govitecan (SG).
  4. A method according to any one of claims 1 to 3, wherein the anti-PD-1 antibody or its antigen-binding fragment comprises a light chain variable region comprising SEQ ID NO. 6 or a variant thereof, and a heavy chain variable region comprising SEQ ID NO. 11.
  5. A method according to any one of claims 1 to 4, wherein the anti-PD-1 antibody or its antigen-binding fragment comprises a light chain comprising SEQ ID NO. 7 and a heavy chain comprising SEQ ID NO. 12.
  6. A method according to any one of claims 1 to 5, wherein the anti-PD-1 antibody or its antigen-binding fragment is pembrolizumab or a variant thereof.
  7. In claim 6, the method wherein the anti-PD-1 antibody or its antigen fragment is pembrolizumab.
  8. A method according to claim 1, wherein the ADC is SG and the anti-PD-1 antibody or its antigen fragment is pembrolizumab.
  9. A method according to any one of claims 1 to 8, wherein the patient has a PD-L1 tumor ratio score (TPS) of 50% or more.
  10. A method according to any one of claims 1 to 8, wherein the patient has a PD-L1 TPS of less than 50%.
  11. A method according to any one of claims 1 to 10, wherein the patient has non-squamous NSCLC.
  12. A method according to any one of claims 1 to 10, wherein the patient has flat NSCLC.
  13. A method according to any one of claims 1 to 12, wherein the method does not include the combined administration of chemotherapy.
  14. In paragraph 13, the above method does not include the combined administration of platinum-based chemotherapy.
  15. A method according to any one of claims 1 to 14, wherein the method does not include the co-administration of an anti-TGIT antibody.
  16. A method according to claim 8, wherein the partial response is a reduction in the size of one or more measurable tumors by about 50% or more from baseline to about 13 weeks or more after baseline.
  17. In paragraph 16, the method wherein the partial response is a reduction in the size of one or more measurable tumors by about 60% or more from baseline to about 13 weeks or more after baseline.
  18. In claim 8, when the above method is used to treat metastatic NSCLC in a patient population with a PD-L1 TPS of 50% or more, the method achieves a partial response rate of about 69% or more.
  19. In claim 8, when the above method is used to treat metastatic NSCLC in a patient population with PD-L1 TPS of less than 50%, the method achieves a partial response rate of about 44% or more.
  20. A method according to claim 8, wherein when treating metastatic NSCLC in a patient population using the above method, the method achieves a partial response of about 56% or more regardless of the PD-L1 TPS status of the patient population.

Description

Treatment of non-small cell lung cancer using sacituzumab govitecan and anti-PD-1 antibodies or their antigen-binding fragments Cross-reference of related applications The present application claims priority to U.S. Provisional Application No. 63/604,632 filed November 30, 2023; U.S. Provisional Application No. 63/592,031 filed October 20, 2023; U.S. Provisional Application No. 63/581,239 filed September 7, 2023; U.S. Provisional Application No. 63/519,818 filed August 15, 2023; and U.S. Provisional Application No. 63/564,626 filed March 13, 2024, all of which are incorporated herein by reference. Integration by reference of the sequence list The present application includes a sequence list submitted as an electronic document in the form of an XML file, the entirety of which is incorporated herein by reference. The XML copy created on August 13, 2024, is named 210196-304006_PCT_SL.xml and has a size of 19,960 bytes. Technology field The present disclosure relates to a method for treating non-small cell lung cancer using sacituzumab govitecan (SG) and an anti-PD-1 antibody or an antigen-binding fragment thereof. Lung cancer (both small and non-small cell) is the second most common cancer in both men and women in the United States (excluding skin cancer). About 10 to 15% of all lung cancers are small cell lung cancer, and about 80 to 85% are non-small cell lung cancer (www.cancer.org). Programmed death (ligand) 1 (PD-[L]1) inhibitor-based regimens are the standard treatment for first-line metastatic non-small cell lung cancer (NSCLC), but additional regimens are needed to further improve outcomes. Sacituzumab govitecan (SG) is an antibody-drug conjugate (ADC) composed of (a) a humanized monoclonal antibody (hRS7) that binds to the cell surface receptor Trop 2, (b) a payload (SN-38) that is a topoisomerase I inhibitor, and (c) a linker (CL2A) that binds the antibody to the payload. In non-small cell lung cancer, Trop 2 is strongly expressed. High expression of Trop 2 in non-small cell lung cancer combined with high unmet needs led to the design of the Phase 2, open-label, multi-cohort, Ph 2 EVOKE-02 study (NCT05186974) evaluating SG + pembrolizumab ± platinum agents as first-line treatment for metastatic NSCLC. SG is marketed under the name TRODELVY and is presented for (1) adult patients with unresectable locally advanced or metastatic HR+/HER2- breast cancer who have received at least two additional systemic therapies in an endocrine-based setting; (2) adult patients with unresectable locally advanced or mTNBC who have received two or more previous systemic therapies, at least one of which was for metastatic disease; and (3) adult patients with locally advanced or mUC who have previously received platinum-containing chemotherapy and one of programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors (limited to accelerated approval). PD-1 is recognized as an important molecule in immune regulation and the maintenance of peripheral tolerance. PD-1 is moderately expressed on naive T, B, and NKT cells and is up-regulated by T/B cell receptor signaling on lymphocytes, monocytes, and myeloid cells (Sharpe, Arlene H et al. , The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nature Immunology (2007); 8:239-245). Two known ligands for PD-1, PD-L1 (B7-H1) and PD-L2 (B7-DC), are expressed in human cancers occurring in various tissues. In large sample sets of cancers, e.g., ovarian cancer, renal cancer, colorectal cancer, pancreatic cancer, liver cancer, and melanoma, PD-L1 expression was shown to correlate with poor prognosis and reduced overall survival regardless of subsequent treatment (References [Dong, Haidong et al. , Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med. 2002 Aug;8(8):793-800]; References [Yang, Wanhua et al. , PD-1 interaction contributes to the functional suppression of T-cell responses to human uveal melanoma cells in vitro. Invest Ophthalmol Vis Sci. 2008 Jun; 49(6 (2008): 49: 2518-2525]; References [Ghebeh, Hazem et al. , The B7-H1 (PD-L1) T lymphocyte-inhibitory molecule is expressed in breast cancer patients with infiltrating ductal carcinoma: correlation with important high-risk prognostic factors. Neoplasia (2006) 8: 190-198]; Hamanishi, Junzo et al ., Programmed cell death 1 ligand 1 and tumor-infiltrating CD8+ T lymphocytes are prognostic factors of human ovarian cancer. Proc. Natl. Acad. Sci. USA (2007): 104: 3360-3365]; Thompson, R Houston, and Eugene D Kwon, Significance of B7-H1 overexpression in kidney cancer. Clinical Genitourin Cancer (2006): 5: 206-211]; Nomi, Takeo et al. , Clinical significance and therapeutic potential of the programmed death-1 ligand/programmed death-1 pathway in human pancreatic cancer. Clinical Cancer Research (2007);13:2151-2157]; Ohigashi, Yuichiro et al. , Clinical significance of programmed death-1 ligand-1 and programmed death-1 ligand