Onyx Therapeutics, Inc.

Onyx Pharmaceuticals, Inc.

Christopher J Kirk

Mark K Bennett

Susan D Demo

Jing Jiang

Tony Muchamuel

Katherine A Chu

Naveen Bejugam

Mouhannad Jumaa

Kevin Kwei

Hansen Wong

Rahul Vishram Manek

Sanjeev Sharma

Jeffrey Joseph Jones

Eric Lowe

Andrea Loehr

Tracey Lin

Ying Fang

Shirin Kapur

Alana Lerner

Elena T Chan

Brian Tuch

Jeremiah Degenhardt

Mouhannad Jamaa

Zhengping Wang

This disclosure provides methods of treating a cancer in a patient using a peptide epoxyketone proteasome inhibitor in combination with a PIM kinase inhibitor.

Peptide epoxyketone proteasome inhibitors in combination with PIM kinase inhibitors for treatment of cancers

Methods of treating a tumor in a subject and methods of determining a treatment regimen for a subject with a tumor are provided herein. In exemplary aspects, the methods comprise measuring the level of expression of immunoglobulin, FCGR2B, a gene listed in Table 4, or a combination thereof. In exemplary aspects, the subject is a subject from which a sample was obtained, wherein the level of immunoglobulin, FCGR2B, a gene listed in Table 4, or a combination thereof, has been measured from the sample. Related kits, computer readable-storage media, systems, and methods implemented by a processor in a computer are further provided.

Immunoglobulin expression levels as biomarker for proteasome inhibitor response

ABSTRACT The invention provides combination therapy, wherein one or more other therapeutic agents are administered agents are administered with peptide epoxyketones or a pharmaceutically acceptable salt thereof. Another aspect of the invention relates to treating cancer with a peptide epoxyketone administered in combination with another therapeutic agent.

Combination therapy with peptide epoxyketones

The invention provides combination therapy, wherein one or more other therapeutic agents are administered agents are administered with peptide epoxyketones or a pharmaceutically acceptable salt thereof. Another aspect of the invention relates to treating cancer with a peptide epoxyketone administered in combination with another therapeutic agent.

Liposomal compositions comprising peptide epoxyketone compounds are described, as well as methods of making and using such liposomal compositions. These liposomal compositions enhance the therapeutic window of peptide epoxyketone compounds by improving in vivo half-life relative to non-liposomal compositions comprising peptide epoxyketone compounds, providing desirable pharmacodynamic profiles, and providing anti-tumor activity in a human tumor xenograft model, greater than or equal to non-liposomal compositions comprising peptide epoxyketone compounds. Further, experiments performed in support of the present invention demonstrated improved tolerability of liposomal compositions comprising peptide epoxyketone compounds.

Liposomal compositions of epoxyketone-based proteasome inhibitors

This disclosure features modified release pharmaceutical formulations (e.g., extended release pharmaceutical formulations; e.g., solid dosage forms, e.g., tablets) that are useful for the oral administration of oprozomib, or a pharmaceutically acceptable salt thereof, to a human or animal subject as well as methods of making and using the formulations.

Modified release formulations for oprozomib

The invention provides a method of repressing metastasis of a cancer compromising the administration of a peptide epoxyketone proteasome inhibitor. Furthermore, the method can be performed in combination with the administration of one or more additional therapeutics.

Use of peptide epoxyketones for metastasis suppression

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San Francisco, CA, United States of America

Christopher J Kirk