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KR-20260066109-A - Methods to treat non-small cell lung cancer

KR20260066109AKR 20260066109 AKR20260066109 AKR 20260066109AKR-20260066109-A

Abstract

The present disclosure provides a method for treating EGFR-positive non-small cell lung cancer (NSCLC) in subjects whose disease has progressed during or after treatment with at least one previous tyrosine kinase inhibitor (TKI).

Inventors

  • 노블라우치, 로랜드 엘마르
  • 바움엘, 조슈아

Assignees

  • 얀센 바이오테크 인코포레이티드

Dates

Publication Date
20260512
Application Date
20240904
Priority Date
20230905

Claims (20)

  1. A method for improving the median progression-free survival (PFS) in a population of subjects with locally advanced or metastatic NSCLC possessing one or more epidermal growth factor receptor (EGFR) mutations in which non-small cell lung cancer (NSCLC) has progressed during or after treatment with at least one prior tyrosine kinase inhibitor (TKI), (i) A therapeutically effective dose of bispecific anti-EGFR/c-Met antibody, (ii) a therapeutically effective amount of carboplatin, and (iii) a step of administering a combination therapy containing a therapeutically effective amount of pemetrexid to a subject population, and The improvement in the median PFS above is compared to the median PFS of a reference population of NSCLC having one or more EGFR mutations, in which NSCLC progressed during or after treatment with at least one previous TKI, wherein the reference population was administered carboplatin and pemetrexid but not the bispecific anti-EGFR/c-Met antibody.
  2. The method according to claim 1, wherein the bispecific anti-EGFR/c-Met antibody comprises a first domain that specifically binds to EGFR and a second domain that specifically binds to c-Met, wherein the first domain comprises heavy chain complementarity determining region 1 (HCDR1) of SEQ ID NO. 1, HCDR2 of SEQ ID NO. 2, HCDR3 of SEQ ID NO. 3, light chain complementarity determining region 1 (LCDR1) of SEQ ID NO. 4, LCDR2 of SEQ ID NO. 5, and LCDR3 of SEQ ID NO. 6, and the second domain that binds to c-Met comprises HCDR1 of SEQ ID NO. 7, HCDR2 of SEQ ID NO. 8, HCDR3 of SEQ ID NO. 9, LCDR1 of SEQ ID NO. 10, LCDR2 of SEQ ID NO. 11, and LCDR3 of SEQ ID NO. 12.
  3. The method of claim 1 or 2, wherein one or more EGFR mutations comprise one or more exon 19 deletions, or exon 21 L858R substitutions, or any combination thereof.
  4. In paragraph 3, the method wherein one or more EGFR mutations comprise one or more exon 19 deletions.
  5. In paragraph 3, the method wherein one or more EGFR mutations comprise an exon 21 L858R substitution.
  6. A method according to any one of claims 1 to 5, wherein at least one prior TKI comprises a first-generation EGFR TKI.
  7. A method according to any one of claims 1 to 5, wherein at least one prior TKI comprises a second-generation EGFR TKI.
  8. A method according to any one of claims 1 to 5, wherein at least one prior TKI comprises a third-generation EGFR TKI.
  9. A method according to any one of claims 1 to 5, wherein at least one prior TKI comprises osimertinib.
  10. A method according to any one of claims 1 to 9, wherein the combination therapy is started on day 1 of cycle 1 of the first 21-day cycle and continued in subsequent 21-day cycles.
  11. A method according to any one of claims 1 to 10, wherein the bispecific anti-EGFR/c-Met antibody is administered intravenously.
  12. A method according to any one of claims 1 to 10, wherein the bispecific anti-EGFR/c-Met antibody is administered subcutaneously.
  13. A method comprising the step of administering a bispecific anti-EGFR/c-Met antibody in an amount of about 140 mg to about 2240 mg in any one of claims 1 to 12.
  14. In paragraph 13, the bispecific anti-EGFR/c-Met antibody is administered at a dose of about 700 mg, about 750 mg, about 800 mg, about 850 mg, 900 mg, 950 mg, 1000 mg, 1050 mg, 1100 mg, 1150 mg, 1200 mg, 1250 mg, 1300 mg, 1350 mg, 1400 mg, 1575 mg, 1600 mg, 1750 mg, 2100 mg, or 2240 mg.
  15. In claim 14, the bispecific anti-EGFR/c-Met antibody is administered at a dose of about 1400 mg on days 1, 8, and 15 of cycle 1 and on day 1 of cycle 2 when the subject's body weight is less than 80 kg.
  16. In claim 15, the bispecific anti-EGFR/c-Met antibody dose for Day 1 of Cycle 1 is administered as a divided dose over Day 1 and Day 2.
  17. In claim 14, the bispecific anti-EGFR/c-Met antibody is administered at a dose of approximately 1750 mg on day 1 of each 21-day cycle, starting from cycle 3, when the subject's body weight is less than 80 kg.
  18. In claim 14, the bispecific anti-EGFR/c-Met antibody is administered at a dose of about 1750 mg on days 1, 8, and 15 of cycle 1 and on day 1 of cycle 2 when the subject's body weight is 80 kg or more.
  19. In claim 18, the bispecific anti-EGFR/c-Met antibody dose for Day 1 of Cycle 1 is administered as a divided dose over Day 1 and Day 2.
  20. In claim 14, the bispecific anti-EGFR/c-Met antibody is administered at a dose of approximately 2100 mg on day 1 of each 21-day cycle, starting from cycle 3, when the subject's body weight is 80 kg or more.

Description

Methods to treat non-small cell lung cancer Cross-reference regarding related applications This application claims priority to U.S. Provisional Application No. 63/536,575 filed September 5, 2023, and U.S. Provisional Application No. 63/564,664 filed March 13, 2024, the disclosures of each of which are incorporated herein by reference in their entirety. Sequence list The present application comprises a sequence list submitted electronically in XML format, the entirety of which is incorporated herein by reference. An XML copy created on September 3, 2024, is named JBI6835_SeqListing.xml and has a size of 20,480 bytes. Technology field The present disclosure provides a method for treating epidermal growth factor receptor (EGFR)-positive non-small cell lung cancer (NSCLC) in subjects whose disease has progressed during or after treatment with at least one prior tyrosine kinase inhibitor (TKI). Stratification of advanced non-small cell lung cancer (NSCLC) based on oncogenic driver mutations has improved overall survival, quality of life, and the efficacy of targeted solid tumor therapies for patients with actionable driver mutations. In NSCLC, specific mutations in the EGFR gene are associated with high response rates to EGFR tyrosine kinase inhibitors (EGFR-TKIs). While most NSCLC patients with EGFR mutations respond to EGFR TKI therapy initially, virtually all acquire resistance that prevents a sustained response. Nearly 60% of all tumors that develop resistance to EGFR tyrosine kinase inhibitors either increase hepatocyte growth factor receptor (c-Met) expression, amplify the c-Met gene, or increase hepatocyte growth factor, its only known ligand (Turke et al., Cancer Cell, 17:77-88, 2010). The progression of acquired resistance to EGFR-TKIs such as osimertinib in epidermal growth factor receptor mutant (EGFRm) NSCLC is likely to result from complex and heterogeneous resistance patterns accompanied by the co-occurrence of multiple resistance mechanisms, making it difficult to identify the details of these mechanisms. Consequently, there are inherent challenges regarding the duration and persistence of response to targeted therapies, and there is still a need for a new treatment paradigm for patients with NSCLC whose disease has progressed during or after treatment with at least one previous tyrosine kinase inhibitor (TKI). In one embodiment, a method for improving the median progression-free survival (PFS) in a population of subjects having locally advanced or metastatic non-small cell lung cancer (NSCLC) with one or more epidermal growth factor receptor (EGFR) mutations that has progressed during or after treatment with at least one prior tyrosine kinase inhibitor (TKI), the method comprises the step of administering a combination therapy comprising (i) a therapeutically effective amount of a bispecific anti-EGFR/c-Met antibody, (ii) a therapeutically effective amount of carboplatin, and (iii) a therapeutically effective amount of pemetrexid to a population of subjects, wherein the improvement in the median PFS is relative to the median PFS of a reference population of subjects having NSCLC with one or more EGFR mutations that has progressed during or after treatment with at least one prior TKI, said reference population having been administered carboplatin and pemetrexid but not said bispecific anti-EGFR/c-Met antibody. In another aspect, a method for improving the median progression-free survival (PFS) in a population of subjects having locally advanced or metastatic non-small cell lung cancer (NSCLC) possessing one or more epidermal growth factor receptor (EGFR) mutations that has progressed during or after treatment with at least one prior tyrosine kinase inhibitor (TKI), the method comprises the step of administering a combination therapy to a population of subjects comprising (i) a therapeutically effective amount of a bispecific anti-EGFR/c-Met antibody, (ii) a therapeutically effective amount of lazertinib, or a pharmaceutically acceptable salt or hydrate thereof, (iii) a therapeutically effective amount of carboplatin, and (iv) a therapeutically effective amount of pemetrexid, wherein the improvement in the median PFS is relative to the median PFS of a reference population of subjects having NSCLC possessing one or more EGFR mutations that has progressed during or after treatment with at least one prior TKI, said reference population received carboplatin and pemetrexid but said bispecific A method is provided herein in which the anti-EGFR/c-Met antibody or the lazertinib or its pharmaceutically acceptable salt or hydrate is not administered. In some embodiments, lazertinib, or its pharmaceutically acceptable salt or hydrate is lazertinib mesylate. In some embodiments, lazertinib, or its pharmaceutically acceptable salt or hydrate is lazertinib mesylate monohydrate. In some embodiments, lazertinib, or its pharmaceutically acceptable salt or hydrate is administered orally at a dose of about 240 mg onc