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EP-4736878-A2 - SATRAPLATIN FOR USE IN THE TREATMENT OF LYMPHOID NEOPLASMS

EP4736878A2EP 4736878 A2EP4736878 A2EP 4736878A2EP-4736878-A2

Abstract

The present invention relates to satraplatin for use in a method of treating a malignancy of the lymphoid tissue in a mammal, preferably a human, and in particular of a malignancy of the lymphoid tissue with primary or secondary central nervous system (CNS) manifestation such as primary diffuse large B cell lymphoma of the CNS.

Inventors

  • RENNER, Christoph Robert
  • ZANDER, Thilo Joachim
  • MARKSON, Gabriel Benjamin
  • DAHM, Felix

Assignees

  • pharma& Schweiz GmbH

Dates

Publication Date
20260506
Application Date
20210608

Claims (20)

  1. Satraplatin for use in treating a lymphoid neoplasm in a mammal, wherein said lymphoid neoplasm is a mature B-cell neoplasm or a mature T-cell neoplasm, wherein said mature B-cell neoplasm or said mature T-cell neoplasm is selected from the group consisting of: mantle cell lymphoma, Burkitt lymphoma, diffuse large B cell lymphoma (DLBCL), secondary CNS lymphoma (SCNSL), primary CNS lymphoma (PCNSL), cutaneous T cell lymphoma (CTCL), and a lymphoma with primary or secondary central nervous system (CNS) manifestation.
  2. Satraplatin for use according to claim 1, wherein said mature B-cell neoplasm is selected from the group consisting of: DLBCL NOS, DLBCL NOS germinal center B cell type (GCB), DLBCL NOS activated B cell type (ABC), and primary DLBCL of the central nervous system (CNS).
  3. Satraplatin for use according to claim 1, wherein said mature B-cell neoplasm is a primary CNS lymphoma (PCNSL).
  4. Satraplatin for use according to any of the preceding claims, wherein said lymphoid neoplasm is a lymphoma with primary or secondary central nervous system (CNS) manifestation.
  5. Satraplatin for use according to any of the preceding claims, wherein said lymphoid neoplasm is primary CNS lymphoma (PCNSL).
  6. Satraplatin for use according to any of the claims 1 or 2, or claim 4, wherein said lymphoid neoplasm is a secondary CNS lymphoma (SCNSL).
  7. Satraplatin for use according to any of the claims 1 to 5, wherein said lymphoid neoplasm is a primary DLBCL of the central nervous system (CNS).
  8. Satraplatin for use according to claim 1, wherein said mature T-cell neoplasm is selected from the group consisting of: Sézary syndrome, and a primary cutaneous CD30+ T cell lymphoproliferative disorder.
  9. Satraplatin for use according to claim 1, wherein said mature T-cell neoplasm is a cutaneous T cell lymphoma (CTCL).
  10. Satraplatin for use according to any one the claims 1 to 9, wherein said satraplatin is formulated for oral administration.
  11. Satraplatin for use according to claim 10, wherein said satraplatin is for administration at a dosage schedule of; a) 60-140mg/m 2 po day 1-5 q 35 days; or b) 60-80 mg/m 2 po day 1-5 q 28 days.
  12. Satraplatin for use according to claim 11, wherein said satraplatin is for administration at a dosage schedule of 80mg/m 2 po day 1-5 q 35 days.
  13. Satraplatin for use according to any preceding claim, wherein said treatment results in killing or inhibition of the growth of tumor cells.
  14. Satraplatin for use according to any preceding claim, wherein said treatment attenuates, ameliorates, or eliminates one or more symptoms of the disease, condition, or disorder.
  15. Satraplatin for use according to any preceding claim, wherein said treatment reduces the number of cancer cells; reduces the tumor size; inhibits cancer cell infiltration into peripheral organs; inhibits tumor metastasis; inhibits tumor growth; and/or relieves one or more of the symptoms associated with the cancer.
  16. Satraplatin for use according to any preceding claim, wherein said treatment results in killing or inhibition of the growth of cancer cells.
  17. Satraplatin for use according to any one of claims 1 to 16, wherein said satraplatin is for administration with one or more additional therapeutic agents.
  18. Satraplatin for use according to claim 17, wherein said satraplatin and the one or more additional therapeutic agents are for co-administration.
  19. Satraplatin for use according to any preceding claim, wherein said mammal is a human.
  20. Satraplatin for use according to any of claims 1-7 or claims 10-19, wherein the lymphoid neoplasm is a C5 type or MCD subtype diffuse large B cell lymphoma (DLBCL).

Description

The present invention relates to satraplatin for use in a method of treating a malignancy of the lymphoid tissue in a mammal, preferably in a human, and in particular of a malignancy of the lymphoid tissue with primary or secondary central nervous system (CNS) manifestation such as primary diffuse large B cell lymphoma of the CNS. RELATED ART Malignancies of the lymphoid tissue are lymphoid neoplasms that derive from the lymphoid cell lines. The lymphoid cell line produces B, T, NK and plasma cells. Well characterised lymphoid neoplasms include lymphoma and multiple myeloma. Lymphomas are tumours that develop from lymphocytes of the lymph glands (lymph nodes) located throughout the body. Albeit forming and maturing in the lymphatic organs, lymphocytes have the physiological task of circulating in the bloodstream and in the various organs of the body in order to detect foreign antigens to be killed. Tumoral lymphocytes retain such capacity to circulate in the body, so that generally lymphomas are widespread throughout the body since their onset, also at a distance from the place of origin. Multiple myeloma affects plasma cells that accumulate in the bone marrow and often also affects several areas of the body, such as the spine, skull, pelvis and ribs. Thus, malignancies of the lymphoid tissue can spread, through the blood and/or lymphatic vessels, from the lymph nodes to other lymph nodes or organs, both lymphatic (bone marrow, spleen, etc.) and extra lymphatic (skin, lungs, central nervous system, stomach, kidney, liver and the like) (Vardiman JW et al. Blood (2009) 114:1787-1797). The WHO classification of hematopoietic and lymphoid tumors and the associated monograph, first published in 2001 and most recently updated in 2016, represent the established guidelines for the diagnosis of malignant lymphomas and multiple myeloma. The WHO classification places an emphasis on cell lineage and classifies the lymphoid neoplasms into the following groups: (i) mature B-cell lymphoid neoplasms, (ii) mature T and NK-cell neoplasms, (iii) Hodgkin lymphomas, (iv) post-transplant lymphoproliferative disorders (PTLD) and (v) histiocytic and dendritic cell neoplasms (Swerdlow SH et al. Blood (2016) 127:2375-2390). Lymphoma and multiple myeloma are mostly incurable diseases requiring long-term, sometimes permanent treatment. The central nervous system (CNS) is an immunologically privileged site which is separated from the circulation by the blood-brain barrier and thus, lymphomas with CNS manifestation including primary or secondary CNS lymphomas are some of the most difficult to treat rare cancer entities. Primary central nervous system lymphoma (PCNSL), which is a highly aggressive non-Hodgkin lymphoma confined to the CNS including the brain, spine, eyes, and leptomeninges without evidence of systemic spread (Grommes C and DeAngelis LM J Clin Oncol (2017) 35:2410-2418), can only be cured in a subset of young/fit patients with extensive (immuno-) chemotherapy (Mendez JS et al. Neuro Oncol (2018) 20:687-694; Houillier C et al. Neurology (2020) 94:1027-1039). More than 70% of all patients relapse within 2 years and will die within 6-9 months after relapse. In addition, the frequency of CNS lymphoma is increasing worldwide with a particular increase in elderly patients (Shiels MS et al. Br J Haematol (2016) 174:417-424). Therefore, the treatment of malignancies of the lymphoid tissues with CNS manifestation, and in particular, the treatment of primary CNS lymphoma is of high unmet medical need. Platinum-based compounds are a mainstay of cancer chemotherapy. Since their original discovery, platinum compounds have emerged as important agents for the therapy of several human malignancies including lung, head and neck, and cervical cancer. There are three platinum compounds that are predominantly used in the current treatment of cancer - cisplatin, carboplatin, and oxaliplatin. As presented in the Physicians' Cancer Chemotherapy Drug Manual (Edward Chu; Vincent T. DeVita Jr.Goyena R, Fallis A. Physicians' Cancer Chemotherapy Drug Manual, 2019) they all belong to the same class of platinum salts, but still they differ considerably in their efficacy, therapeutic use, pharmacokinetics, adverse effect profile and administration route. Cisplatin is a cornerstone drug in cancer treatment. However, its use is usually limited due to severe, dose-limiting adverse effects such as neurotoxicity, ototoxicity and renal toxicity. Moreover, cisplatin has to be administered intravenously (Bhargava A and Vaishampayan UN Expert Opin Investig Drugs (2009) 18:1787-1797; Akshintala S et al. Pediatr Blood Cancer (2015) 62:603-610).These disadvantages limit the use of cisplatin to certain patient populations and disease indications. There is a real need for novel treatment options for cancer patients including those with lymphoid neoplasms such as lymphoma or multiple myeloma. SUMMARY OF THE INVENTION Satraplatin has been developed and emerged as an or