Novel use of an inhibitor of the poly-adp ribose polymerase (parp) in the treatment of cancer
AssigneeTesaro, Inc.
InventorsTsz cheong NG, Anna PASTO, Ali Raza AWAN
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Abstract
The present invention relates to methods for personalizing cancer treatment using information obtained from patient derived organoids. Personalized treatment regimens can be identified using IC50 values (measured in organoid tumor cells alone), ratio of cell viability between tumor cells treated with a PARP inhibitor and DMSO (measured in the presence of immune cells), the length of DNA in exosomal DNA-chromatin complex identified from treatment of patient derived organoids with platinum therapy or a PARP inhibitor, or by responses to previous therapies.
Claims20
-25. (canceled)
A method for identifying a suitable treatment regimen for a human patient having cancer comprising either:
- a) calculating the ratio (PARP inhibitor/DMSO) in tumour cell viability of a patient derived organoid generated from said cancer;
- and
- b) identifying a suitable treatment regimen based on the sensitivity of the patient derived organoid to a PARP inhibitor wherein the ratio (PARP inhibitor/DMSO) in tumour cell viability is <0.75, the suitable treatment regimen comprises treatment a PARP inhibitor, and wherein the ratio (PARP inhibitor/DMSO) in tumour cell viability is >0.75, the suitable treatment regimen comprises stepwise treatment with a PARP inhibitor, followed by treatment with a PD1 or PD-L1 inhibitor;
- or
- a) determining the ratio (PARP inhibitor/DMSO) of exosomal DNA length following treatment of a patient derived organoid with a PARP inhibitor or DMSO;
- and
- b) identifying a suitable treatment regimen based on the ratio (PARP inhibitor/DMSO) of exosomal DNA length, wherein the ratio (niraparib/DMSO)>1.1, the suitable treatment regimen comprises treatment with a PARP inhibitor, and wherein the ratio (PARP inhibitor/DMSO)<1.1, the suitable treatment regimen comprises stepwise treatment with a PARP inhibitor, followed by treatment with a PD1 or PD-L1 inhibitor.
A method of treating cancer in a patient in need thereof comprising:
- a. administering a PARP inhibitor to the patient, wherein the patient has a tumour cell viability ratio (PARP inhibitor/DMSO) of <0.75;
- or
- b. administering a PARP inhibitor followed by treatment with a PD1 or PD-L1 inhibitor to the patient, wherein the patient has a tumour cell viability ratio (PARP inhibitor/DMSO) of >0.75;
- wherein a tumour cell viability ratio (PARP inhibitor/DMSO) is calculated from a patient derived organoid generated from said cancer.
A method of treating cancer in a patient in need thereof comprising:
- a. administering a PARP inhibitor to the patient, wherein the patient has an exosomal DNA length ratio (PARP inhibitor/DMSO) of >1.1;
- or
- b. administering a PARP inhibitor followed by treatment with a PD1 or PD-L1 inhibitor to the patient, wherein the patient has an exosomal DNA length ratio (PARP inhibitor/DMSO) of <1.1;
- wherein an exosomal DNA length ratio is determined following treatment of a patient derived organoid with a PARP inhibitor or DMSO
A method for treating cancer in a human patient being treated with a PARP inhibitor, comprising administering a therapeutically effective amount of PD1 or PD-L1 inhibitor to the patient wherein the exosomal DNA ratio (post-treatment with a PARP inhibitor/pre treatment with a PARP inhibitor) in a blood sample from the patient is <1.1.
Dependencies are inferred from the claim text.