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KR-20260068129-A - METHODS AND COMPOSITIONS FOR DOSING OF ALLOGENEIC CHIMERIC ANTIGEN RECEPTOR T CELLS

KR20260068129AKR 20260068129 AKR20260068129 AKR 20260068129AKR-20260068129-A

Abstract

The present disclosure relates to a dosage for the treatment of human patients who are susceptible to or diagnosed with diseases such as cancer. A method for administering chimeric antigen receptor (CAR)-T cells is provided. Additionally, a composition and a manufactured article for use in said method are provided.

Inventors

  • 콘토 시릴 알키스
  • 지나이 아미나

Assignees

  • 알로젠 테라퓨틱스 인코포레이티드
  • 르 라보레또레 쎄르비에르

Dates

Publication Date
20260513
Application Date
20181030
Priority Date
20171031

Claims (20)

  1. A method for treating a subject suffering from refractory and/or relapsed non-Hodgkin lymphoma, wherein the method comprises the step of administering at least one dose of allogeneic chimeric antigen receptor (CAR)-T cells (CAR-T cells) comprising anti-human CD19 4-1BB/CD3 zeta CAR to the subject, wherein the at least one dose is about 20 x 10⁶ cells/dose to about 360 x 10⁶ cells/dose.
  2. In paragraph 1, the non-Hodgkin lymphoma is a large B-cell lymphoma.
  3. In paragraph 1, the method wherein the non-Hodgkin lymphoma is a follicular lymphoma.
  4. A method according to any one of claims 1 to 3, wherein at least one dose is selected from the group consisting of about 20 x 10⁶ cells/dose, about 40 x 10⁶ cells/dose, about 80 x 10⁶ cells/dose, about 120 x 10⁶ cells/dose, about 240 x 10⁶ cells/dose, and about 360 x 10⁶ cells/dose.
  5. A method according to any one of claims 1 to 4, wherein at least one dose is selected from the group consisting of about 20 x 10⁶ cells/dose, about 80 x 10⁶ cells/dose, and about 240 x 10⁶ cells/dose, when the body weight of the subject is 50 kg or less.
  6. A method according to any one of claims 1 to 4, wherein at least one dose is selected from the group consisting of about 20 x 10⁶ cells/dose, about 40 x 10⁶ cells/dose, about 120 x 10⁶ cells/dose and about 360 x 10⁶ cells/dose when the body weight of the subject exceeds 50 kg.
  7. A method according to any one of claims 1 to 6, wherein the CAR-T cells are deficient in CD52.
  8. A method according to any one of claims 1 to 6, wherein the CAR-T cells comprise a mixture of CD52-deficient cells and CD-52-positive cells.
  9. A method according to any one of claims 1 to 8, wherein the CAR-T cell comprises the CAR of SEQ ID NO. 1.
  10. A method according to any one of claims 1 to 9, wherein the CAR-T cells comprise UCART19(CD19)CAR/RQR8+_TCRαβ-_T-cells.
  11. A method according to any one of claims 1 to 9, wherein the CAR-T cells do not express a safety switch.
  12. A method according to any one of claims 1 to 11, wherein CAR expression can be detected in a subject for at least up to 14 days after administration of CAR-T cells.
  13. A method according to any one of claims 1 to 12, wherein CAR expression can be detected in a subject for at least up to 28 days after administration of CAR-T cells.
  14. A method according to any one of claims 1 to 13, wherein the subject exhibits a CR or Cri status for at least one month after CAR-T administration.
  15. A method according to any one of claims 1 to 14, wherein the subject exhibits a CR or Cri status for at least 2 months after CAR-T administration.
  16. A method according to any one of claims 1 to 15, wherein the subject exhibits a CR or Cri status for at least 6 months after CAR-T administration.
  17. A method according to any one of claims 1 to 16, wherein the subject exhibits a CR or Cri status for at least 12 months after CAR-T administration.
  18. A method according to any one of claims 1 to 17, wherein the subject receives primary lymphocyte depletion therapy prior to the administration of at least one dose.
  19. In claim 18, the primary lymphocyte depletion therapy comprises the step of administering fludarabine and cyclophosphamide.
  20. In claim 18, the primary lymphocyte depletion therapy comprises the step of administering fludarabine, cyclophosphamide, and an anti-CD52 antibody.

Description

Methods and compositions for dosing of allogeneic chimeric antigen receptor T cells Cross-reference regarding related applications This application claims priority to U.S. Provisional Application No. 62/750,215 filed October 24, 2018; U.S. Provisional Application No. 62/716,898 filed August 9, 2018; and U.S. Provisional Application No. 62/579,426 filed October 31, 2017, each of which is incorporated herein by reference in its entirety for all purposes. Technology field The present disclosure relates to a therapeutic regimen for the treatment of disorders including proliferative disorders and immune disorders. The therapeutic regimen comprises administering a single dose or multiple doses of immune cells, including allogeneic chimeric antigen receptor T cells. The therapeutic regimen may be used for the prevention and/or treatment of disorders including cancer. Description of the electronically submitted text file The contents of the text file submitted electronically together with the present invention are incorporated by reference in their entirety: a copy of the sequence listing in a computer-readable format (filename: ALGN-012-03WO Sequence Listing.txt, recorded on October 30, 2018, file size is 39,283 bytes). Various methods can be utilized for adoptive cell therapy using engineered cells expressing recombinant receptors, such as chimeric antigen receptor (CAR)-T cells. However, the dose of allogeneic CAR-T cells required to be effective in treating disease and achieving remission in human patients is unknown. Methods, compositions, and manufactured articles for administering and re-administering allogeneic CAR-T cells are provided herein. The disclosed methods reduce the risk of toxicity and/or increase efficacy, for example, by increasing the subject's exposure to the administered cells (e.g., by improving the swelling and/or persistence of the administered cells). The present disclosure relates to a therapeutic regimen for treating disorders such as cancer. More specifically, the present disclosure relates to a therapeutic regimen for treating disorders such as cancer by administering allogeneic CAR-T cells. Features of the method, including the timing of administration and the number of cells administered, provide various advantages, such as, for example, improved efficacy and/or reduced toxicity resulting from exposing the subject to the administered cells. For example, a method for administering CAR-T cells to a subject to treat a disease and/or disorder in the subject is provided. The method generally comprises the steps of administering a single dose or multiple doses of such cells, and/or administering a subsequent dose to a subject who has previously been treated with a previous (e.g., primary) dose of such cells. Additionally, cells, compositions, and manufactured articles for use in this method are provided. In some embodiments, the method comprises the step of treating an adult subject with refractory and/or relapsed CD19+ B-cell acute lymphoblastic leukemia, wherein the method comprises the step of administering at least one dose of an allogeneic chimeric antigen receptor (CAR-T cell) comprising an anti-human CD19 4-1BB/CD3 zeta CAR (e.g., UCART19 (CD19CAR/RQR8+_TCRαβ-_T-cell)) to the subject, wherein the at least one dose is selected from the group consisting of about 6 x 10⁵ cells/dose, about 6 x 10⁶ cells/dose, about 6 to 8 x 10⁷ cells/dose, and about 1.8 to 2.4 x 10⁸ cells/dose. In some embodiments, the method comprises the step of treating a pediatric subject with refractory and/or relapsed CD19+ B-cell acute lymphoblastic leukemia, and the method comprises the step of administering to the subject at least one dose of an allogeneic chimeric antigen receptor (CAR-T cell) comprising an anti-human CD19 4-1BB/CD3 zeta CAR (e.g., UCART19 (CD19CAR/RQR8+_TCRαβ-_T-cell) or UCART19 (CD19CAR/TCRαβ-_T-cell) or UCART19 (CD19CAR/TCRαβ-_T-cell), wherein the at least one dose is about 2 to 8 x 10⁷ cells/dose. In some embodiments, the method comprises the step of treating a subject with refractory and/or relapsed non-Hodgkin lymphoma (e.g., large B-cell lymphoma or follicular lymphoma), and the method comprises the step of administering to the subject at least one dose of an allogeneic chimeric antigen receptor (CAR-T cell) comprising an anti-human CD19 4-1BB/CD3 zeta CAR (CD19CAR/RQR8+_TCRαβ-_T-cell), wherein the at least one dose is about 20 x 10⁶ cells/dose to about 360 x 10⁶ cells/dose, e.g., about 20 x 10⁶ cells/dose, about 40 x 10⁶ cells/dose, about 80 x 10⁶ cells/dose, about 120 x 10⁶ cells/dose, 240 x 10⁶ cells/dose, or about 360 x 10⁶ 6 cells/dosage. In some embodiments, the method comprises: (a) administering a first dose of allogeneic CAR-T cells to a subject with a disease; and (b) administering a subsequent dose of allogeneic CAR-T cells to the subject. In other embodiments, the method is performed by administering the dose of step (b) or the subsequent dose to the subject, said subject