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KR-20260064750-A - Skin Melanoma Treatment Methods

KR20260064750AKR 20260064750 AKR20260064750 AKR 20260064750AKR-20260064750-A

Abstract

The present disclosure provides a method for treating cutaneous melanoma in a subject, comprising the step of administering to the subject a composition comprising a heteromeric TCR-anti-CD3 antibody fusion molecule as a treatment regimen, wherein the treatment regimen comprises administering: (i) a first dose comprising 2 to 30 μg of a TCR-anti-CD3 antibody fusion molecule, (ii) a second dose comprising 5 to 60 μg of a TCR-anti-CD3 antibody fusion molecule, and (iii) a maintenance dose comprising 15 to 200 μg of a TCR-anti-CD3 antibody fusion molecule, wherein the maintenance dose is administered in at least three stages, the first stage is administered once every 6 to 8 days, the second stage is administered once every 12 to 16 days, and the third stage is administered once every 26 to 30 days, and the method is a primary treatment regimen.

Inventors

  • 아베딘, 샤드
  • 다르, 무하마드
  • 위앤, 위앤
  • 먼디, 르네
  • 버먼, 데이비드

Assignees

  • 이뮤노코어 리미티드

Dates

Publication Date
20260507
Application Date
20240731
Priority Date
20230801

Claims (20)

  1. A method for treating cutaneous melanoma in a subject, comprising the step of administering to the subject a composition containing a heteromeric TCR-anti-CD3 antibody fusion molecule as a dosing regimen. Herein, the heteromeric TCR-anti-CD3 antibody fusion molecule comprises (a) an alpha chain amino acid sequence having at least 90%, at least 95%, or 100% identity with the amino acid sequence of SEQ ID NO. 14, and (b) a beta chain amino acid sequence having at least 90%, at least 95%, or 100% identity with the amino acid sequence of SEQ ID NO. 16, wherein the alpha chain comprises a complementarity determining region (CDR) comprising alpha chain CDRs 1, 2, and 3 having the amino acid sequences of SEQ ID NOs. 3, 4, and 5, respectively, and the beta chain comprises beta chain CDRs 1, 2, and 3 having the amino acid sequences of SEQ ID NOs. 9, 10, and 11, respectively. Here, the above administration regimen is: (i) a first dose comprising 2 to 30 µg of a TCR-anti-CD3 antibody fusion molecule, (ii) a second dose comprising 5 to 60 μg of a TCR-anti-CD3 antibody fusion molecule, and (iii) administering a maintenance dose comprising 15 to 200 μg of a TCR-anti-CD3 antibody fusion molecule, wherein the maintenance dose is administered in at least three stages, the first stage is administered once every 6 to 8 days, the second stage is administered once every 12 to 16 days, and the third stage is administered once every 26 to 30 days; and Here, the second dose contains a larger amount of TCR-anti-CD3 antibody fusion molecules than the first dose, and the maintenance dose contains a larger amount of TCR-anti-CD3 antibody fusion molecules than the second dose, The above method is a primary treatment method.
  2. A method according to claim 1, wherein the first dose comprises 2 to 4 μg of TCR-anti-CD3 antibody fusion molecules, the second dose comprises 5 to 14 μg of TCR-anti-CD3 antibody fusion molecules, and the maintenance dose comprises 15 to 55 μg of TCR-anti-CD3 antibody fusion molecules.
  3. A method according to claim 2, wherein the first dose comprises 3 μg of a TCR-anti-CD3 antibody fusion molecule, the second dose comprises 10 μg of a TCR-anti-CD3 antibody fusion molecule, and the maintenance dose comprises 40 μg of a TCR-anti-CD3 antibody fusion molecule.
  4. A method according to claim 1, wherein the first dose comprises 15 to 40 μg of TCR-anti-CD3 antibody fusion molecules, the second dose comprises 30 to 80 μg of TCR-anti-CD3 antibody fusion molecules, and the maintenance dose comprises 140 to 200 μg of TCR-anti-CD3 antibody fusion molecules.
  5. A method according to claim 4, wherein the first dose comprises 20 μg of a TCR-anti-CD3 antibody fusion molecule, the second dose comprises 40 μg of a TCR-anti-CD3 antibody fusion molecule, and the maintenance dose comprises 160 μg of a TCR-anti-CD3 antibody fusion molecule.
  6. A method according to any one of claims 1 to 5, wherein the alpha chain amino acid sequence has 100% identity with the amino acid sequence of SEQ ID NO. 14.
  7. A method according to any one of claims 1 to 6, wherein the beta chain amino acid sequence has 100% identity with the amino acid sequence of SEQ ID NO. 16.
  8. A method according to any one of claims 1 to 7, wherein the first dose is administered once every 7 days.
  9. A method according to any one of claims 1 to 8, wherein the first dose is administered for 1 week to about 3 weeks.
  10. In claim 9, the method wherein the first dose is administered for one week.
  11. A method according to any one of claims 1 to 10, wherein the second dose is administered 6 to 8 days after the first dose.
  12. A method according to any one of claims 1 to 11, wherein the second dose is administered once every 7 days.
  13. A method according to any one of claims 1 to 12, wherein the second dose is administered for 1 week to about 3 weeks.
  14. In paragraph 13, the method wherein the second dose is administered for one week.
  15. A method according to any one of claims 1 to 14, wherein the maintenance dose in the first step is administered 6 to 8 days after the second dose.
  16. A method according to any one of claims 1 to 15, wherein the maintenance dose in the first step is administered once a week.
  17. A method according to any one of claims 1 to 16, wherein the first step is about 2 weeks to about 101 weeks.
  18. In paragraph 17, the method wherein the first step is about 8 weeks to about 14 weeks.
  19. In paragraph 18, the above-mentioned first step is 10 weeks, method.
  20. A method according to any one of claims 1 to 19, wherein the maintenance dose in the second step is administered once every two weeks.

Description

Skin Melanoma Treatment Methods The present disclosure provides a method for treating cutaneous melanoma in a subject, comprising the step of administering to the subject a composition comprising a heteromeric TCR-anti-CD3 antibody fusion molecule as a treatment regimen, wherein the treatment regimen comprises administering: (i) a first dose comprising 2 to 30 μg of a TCR-anti-CD3 antibody fusion molecule, (ii) a second dose comprising 5 to 60 μg of a TCR-anti-CD3 antibody fusion molecule, and (iii) a maintenance dose comprising 15 to 200 μg of a TCR-anti-CD3 antibody fusion molecule, wherein the maintenance dose is administered in at least three stages, the first stage is administered once every 6 to 8 days, the second stage is administered once every 12 to 16 days, and the third stage is administered once every 26 to 30 days, and the method is a primary treatment regimen. Melanoma is a malignant transformation of melanocytes. Although it accounts for about 1% of all skin cancers, it has the highest mortality rate among all skin cancers. Historically, melanoma treatment has been limited to chemotherapy and non-specific immunotherapies, which exhibit poor cure rates and high toxicity. However, the past decade has led to the development of targeted therapies and specific immunotherapies that have transformed the landscape of advanced melanoma treatment. Despite significant progress in understanding the clinical significance of these agents, randomized clinical trials directly comparing their efficacy are rare, and the introduction of these agents is often associated with various dermatological adverse events. Current recommended first-line treatment for unresectable or metastatic disease includes anti-PD-1-based therapy and is considered the standard of care (SoC) for initial treatment. Despite these options, at least half of these subjects experience disease progression within one year. Preferred antigens in melanoma (PRAME) are attractive targets in cancer immunotherapy because they are the most widely expressed cancer-tested antigens (CTAs) that are homogeneously expressed in a large number of tumors. PRAME is an early identified CTA in metastatic cutaneous melanoma. IMC-F106C is the first T-cell receptor (TCR) bispecific protein targeting CD3 and PRAME. In some aspects, the technology described herein relates to a method for treating cutaneous melanoma in a subject, comprising the step of administering to a subject a composition comprising a heterodimeric TCR-anti-CD3 antibody fusion molecule as a dosing regimen, wherein the heterodimeric TCR-anti-CD3 antibody fusion molecule comprises (a) an alpha chain amino acid sequence having at least 90%, at least 95%, or 100% identity with the amino acid sequence of SEQ ID NO. 14, and (b) a beta chain amino acid sequence having at least 90%, at least 95%, or 100% identity with the amino acid sequence of SEQ ID NO. 16, wherein the alpha chain comprises a complementarity determining region (CDR) comprising alpha chain CDR 1, 2, and 3 having the amino acid sequences of SEQ ID NOs. 3, 4, and 5, respectively, and the beta chain comprises beta chain CDR 1, 2, and 3 having the amino acid sequences of SEQ ID NOs. 9, 10, and 11, respectively, wherein the dosing regimen comprises: (i) 2 to 30 The method comprises administering a first dose containing µg of a TCR-anti-CD3 antibody fusion molecule, (ii) a second dose containing 5 to 60 μg of a TCR-anti-CD3 antibody fusion molecule, and (iii) a maintenance dose containing 15 to 200 μg of a TCR-anti-CD3 antibody fusion molecule, wherein the maintenance dose is administered in at least three stages, the first stage is administered once every 6 to 8 days, the second stage is administered once every 12 to 16 days, and the third stage is administered once every 26 to 30 days; wherein the second dose contains a larger amount of a TCR-anti-CD3 antibody fusion molecule than the first dose, and the maintenance dose contains a larger amount of a TCR-anti-CD3 antibody fusion molecule than the second dose, and wherein the method is a primary treatment. In some aspects, the technology described herein relates to a method, wherein a first dose comprises 2 to 4 μg of TCR-anti-CD3 antibody fusion molecules, a second dose comprises 5 to 14 μg of TCR-anti-CD3 antibody fusion molecules, and a maintenance dose comprises 15 to 55 μg of TCR-anti-CD3 antibody fusion molecules. In some aspects, the technology described herein relates to a method, wherein a first dose comprises 3 μg of TCR-anti-CD3 antibody fusion molecules, a second dose comprises 10 μg of TCR-anti-CD3 antibody fusion molecules, and a maintenance dose comprises 40 μg of TCR-anti-CD3 antibody fusion molecules. In some aspects, the technology described herein relates to a method, wherein a first dose comprises 15 to 40 μg of TCR-anti-CD3 antibody fusion molecules, a second dose comprises 30 to 80 μg of TCR-anti-CD3 antibody fusion molecules, and a maintenance dose comprises 140 to 200