Predictive biomarker for hypoxia-activated prodrug therapy
AssigneeMerck Patent GmbH
InventorsBrian A. Elenbaas, Lei A. Shen
Life of this patent
Estimating the term…
Abstract
CYP2W1 levels are predictive of the probability that a cancer patient will respond favorably to cancer therapy involving administration of a hypoxia-activated achiral phosphoramidate mustards.
Claims15
A method for treating cancer in a patient, comprising the steps of determining that a CYP2W1 RNA or protein level in a cancer sample isolated from said patient exceeds a predetermined level and administering to said patient a hypoxia-activated prodrug of formula (I)
- wherein Z3 is selected from the group consisting of:
- and X4 is Cl or Br, or a physiologically acceptable salt thereof.
A kit for determining if a hypoxia-activated prodrug therapy is suitable for treatment of a cancer patient with a hypoxia-activated prodrug of formula (I)
- wherein Z3 is selected from the group consisting of:
- and X4 is Cl or Br, or a physiologically acceptable salt thereof,
- comprising means for determining the CYP2W1 RNA or protein level in a sample isolated from the patient and instructions for use, wherein determination of a high CYP2W1 level indicates increased progression free survival or overall survival when the patient is treated with said prodrug.
A method for advertising a hypoxia-activated prodrug of formula (I)
- wherein Z3 is selected from the group consisting of:
- and X4 is Cl or Br, or a physiologically acceptable salt thereof,
- to a target audience, the use of said prodrug for treating a patient with cancer based on expression of CYP2W1 biomarker.
A method for predicting the likelihood that a patient suffering from cancer, who is a candidate for treatment with a hypoxia-activated prodrug of formula (I)
- wherein Z3 is selected from the group consisting of:
- and X4 is Cl or Br, or a physiologically acceptable salt thereof,
- will respond to the treatment with said prodrug, comprising the determination of the expression level of a prognostic gene or expression product thereof, which is CYP2W1, in a cancer sample obtained from said patient, wherein a higher expression, as compared to a predetermined value, indicates that the patient is likely to respond to said treatment.
A method for monitoring the likelihood of response to a treatment of cancer, which is mediated and/or propagated by hypoxia, wherein the CYP2W1 RNA or protein level is determined in a cancer sample withdrawn from a patient in need of such treatment with a hypoxia-activated prodrug of formula (I)
- wherein Z3 is selected from the group consisting of:
- and X4 is Cl or Br, or a physiologically acceptable salt thereof, administered to said patient, wherein a decrease in CYP2W1 relative to a predetermined level of CYP2W1 in a cancer sample indicates an increased likelihood that said mammal responds to the treatment with said hypoxia-activated prodrug.
An in-vitro method for predicting the likelihood that a patient suffering from cancer will respond therapeutically to the treatment with a hypoxia-activated prodrug of formula (I)
- wherein Z3 is selected from the group consisting of:
- and X4 is Cl or Br, or a physiologically acceptable salt thereof,
- comprising the steps of (i) measuring in a biopsy tissue sample from tumor tissue or plasma of said patient the expression level of CYP2W1 biomarker on protein basis, (ii) exposing ex-vivo a tissue sample from tumor or plasma of said patient to said prodrug, and (iii) measuring in said exposed tissue sample of step (ii) the expression level of said biomarker specified in step (i) along with calculating the differences in expression levels measured in steps (i) and (iii), wherein a decrease in the expression level of said biomarker obtained in this step (iii) compared to step (i) indicates an increased likelihood that said patient will respond therapeutically to the treatment with said prodrug.
15-16. (canceled)
Dependencies are inferred from the claim text.