Glucocorticoid receptor modulators to treat cervical cancer
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Publication Number
US-12285425-B2
Publication Date
2025-04-29
Expiration Date
Abstract
Methods for treating a subject having a cancerous tumor are disclosed. The methods comprise administering to the subject an effective amount of a non-steroidal selective glucocorticoid receptor modulator (SGRM) and an effective amount of a chemotherapeutic agent. The tumor may be cervical cancer. The SGRM may be a fused azadecalin. In embodiments, the SGRM may be a heteroaryl ketone fused azadecalin or an octahydro fused azadecalin.
Core Innovation
The invention relates to treating a subject hosting a cervical cancer tumor by administering an effective amount of a chemotherapeutic agent and an effective amount of a non-steroidal selective glucocorticoid receptor modulator (SGRM) to reduce the tumor load of the cervical cancer tumor. The chemotherapeutic agent is an antimicrotubule agent.
The SGRM is defined as a fused azadecalin compound, including embodiments characterized as an octahydro fused azadecalin compound and other specified fused azadecalin structural constraints. The document also includes approaches to evaluate glucocorticoid receptor (GR) and SGRM characteristics, including selectivity and GR antagonism.
The combined administration with the fused azadecalin SGRM is presented as a strategy to reduce tumor load in cervical cancer tumors, with evaluation frameworks including biomarkers, RECIST clinical response categories, imaging-based assessment using CT and 18F-FDG PET, and an in vivo tumor-growth study framework in a cervical cancer tumor model context.
Claims Coverage
The independent claims cover combination treatment of cervical cancer tumors using a non-steroidal selective glucocorticoid receptor modulator (SGRM) together with a chemotherapeutic agent that is an antimicrotubule agent. The inventive features center on the tumor type, the dual administration, and the structural definitions of the SGRM in fused azadecalin and octahydro fused azadecalin forms.
Combination therapy for reducing tumor load in cervical cancer
A method of treating a subject hosting a cervical cancer tumor comprising administering to the subject an effective amount of a chemotherapeutic agent and an effective amount of a non-steroidal selective glucocorticoid receptor modulator (SGRM) to reduce the tumor load of the cervical cancer tumor.
Fused azadecalin SGRM defined by a specified formula
The method wherein the SGRM is a fused azadecalin compound having the formula defined with parameters, and salts thereof.
Antimicrotubule chemotherapeutic agent
The method wherein said chemotherapeutic agent is an antimicrotubule agent.
Octahydro fused azadecalin SGRM defined by an octahydro fused azadecalin formula
The method wherein the SGRM is an octahydro fused azadecalin compound having the formula defined with parameters, and salts thereof.
Taxane or vinca alkaloid chemotherapeutic agent
The antimicrotubule agent is selected from taxanes, vinca alkaloids, or combinations thereof, including specified compounds and variants.
Overall, the claims cover reducing cervical cancer tumor load by combining an antimicrotubule chemotherapeutic agent with a non-steroidal selective glucocorticoid receptor modulator (SGRM) specified as a fused azadecalin compound. The claim set further refines the SGRM definition into specified fused azadecalin and octahydro fused azadecalin structural formulas, with dependent claims narrowing the chemotherapeutic agent to taxanes or vinca alkaloids and listing specific compounds or variants.
Stated Advantages
Improved tumor-load reduction when a glucocorticoid receptor modulator compound, including CORT125134, is combined with paclitaxel and other chemotherapies.
Reduces the tumor load of the cervical cancer tumor.
Documented Applications
Treating a subject hosting a cervical cancer tumor by administering an SGRM with an antimicrotubule chemotherapeutic agent to reduce tumor load, including a patient case using an SGRM with nab-paclitaxel for cervical cancer with tumor reduction by imaging.
Treating a subject hosting a cervical cancer tumor using a chemotherapeutic agent and a non-steroidal selective glucocorticoid receptor modulator (SGRM) combination.
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