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Method of treating malignant rhabdoid tumor of the ovary (MRTO)/small cell cancer of the ovary of the hypercalcemic type (SCCOHT) with an EZH2 inhibitor

A malignant rhabdoid, hypercalcemia technique for the treatment of malignant rhabdoid tumor of the ovary (MRTO)/small cell carcinoma of the ovary hypercalcemia (SCCOHT) with EZH2 inhibitors

Active Publication Date: 2018-07-31
EPIZYME
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0004] There is a long-standing unmet need for the effective treatment of certain cancers caused by genetic alterations or loss of function of subunits of the SWI / SNF chromatin remodeling complex leading to EZH2-dependent tumorigenesis

Method used

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  • Method of treating malignant rhabdoid tumor of the ovary (MRTO)/small cell cancer of the ovary of the hypercalcemic type (SCCOHT) with an EZH2 inhibitor
  • Method of treating malignant rhabdoid tumor of the ovary (MRTO)/small cell cancer of the ovary of the hypercalcemic type (SCCOHT) with an EZH2 inhibitor
  • Method of treating malignant rhabdoid tumor of the ovary (MRTO)/small cell cancer of the ovary of the hypercalcemic type (SCCOHT) with an EZH2 inhibitor

Examples

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example

[0158] In order that the invention disclosed herein may be more effectively understood, the following examples are provided. It should be understood that these examples are for illustrative purposes only and should not be construed as limiting the disclosure in any way.

example 1

[0159] Example 1: Treatment of SMARCA4-negative MRTO / SCCOHT with tazemetostat

[0160] A 27-year-old human female diagnosed with SMARCA4-negative MRTO / SCCOHT was successfully treated with oral tablet twice-daily (BID) administration of 1600 mg EPIZ-6438 (Tazemetostat). Tumor size decreased from baseline after 8 weeks of treatment and further decreased from 8-week measurements after 16 weeks of treatment.

[0161] The subject was diagnosed with SMARCA4-negative MRTO / SCCOHT in 2013. Throughout 2014, subjects were treated with a course of cisplatin / cyclophosphamide / doxorubicin / etoposide followed by a course of carboplatin / etoposide / cyclophosphamide. None of the treatments were successful. The subject then underwent autologous hematopoietic cell transplantation, which also failed to treat SMARCA4-negative MRTO / SCCOHT.

[0162] Subjects are currently undergoing therapy with 1600 mg tazemetostat administered twice daily (BID) with oral tablets. Figure 6A Preliminary results are...

example 2

[0163] Example 2: Remission of INI1 and SMARCA4 negative tumors

[0164] Treatment of INI1 and SMARCA4-negative tumors with tazemetostat induces pharmacodynamic inhibition of HeK27me3 in tumor tissues.

[0165] Evaluation of MRT and MRTO / SCCOHT clinical activity after tazemetostat treatment showed stable disease for at least 6 months, partial response or complete response.

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Abstract

The disclosure provides a method of treating a malignant rhabdoid tumor in a subject in need thereof including administering to the subject a therapeutically-effective amount of an enhancer of a zestehomolog 2 (EZH2) inhibitor. In certain embodiments of this method the malignant rhabdoid tumor is small cell cancer of the ovary of the hypercalcemic type (SCCOHT) and the EZH2 inhibitor is tazemetostat (also known as Tazemetostat).

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of priority to U.S. Provisional Application No. 62 / 233,146, filed September 25, 2015, and U.S. Provisional Application No. 62 / 252,188, filed November 6, 2015, the contents of each of which are incorporated by reference in their entirety combined here. technical field [0003] The present disclosure relates to the fields of small molecule therapy, cancer, and methods of treating rare cancer types. Background technique [0004] There is a longstanding unmet need for effective treatment of certain cancers caused by genetic alterations or loss of function of subunits of the SWI / SNF chromatin remodeling complex that lead to EZH2-dependent tumorigenesis. Contents of the invention [0005] The present disclosure provides effective treatment for INI1 negative and SMARCA4 negative tumors such as malignant rhabdoid tumor (MRT) and epithelioid sarcoma. INI1 and SMARCA4 are key proteins of t...

Claims

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Application Information

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IPC IPC(8): C07D405/14C07D211/86
CPCA61K45/06A61K31/5377A61K31/4412A61K31/4545A61K31/496A61K31/4436A61K31/4468A61K31/501A61P35/00A61K31/445A61K31/44A61K31/506G01N33/6854G01N33/6893
Inventor 海克·凯尔哈克
Owner EPIZYME
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