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A drug designed to switch off a protein that helps cancer cells survive chemotherapy. Two large trials found it added nothing.
Clusterin is a chaperone protein that rises after apoptotic stress, including chemotherapy, and is associated with treatment resistance. Custirsen is a second-generation antisense oligonucleotide that blocks its production, and the hypothesis was that it would re-sensitise prostate cancer to taxanes.
A randomised phase 2 trial (CUOG P-06c, 42 men) reported encouraging pain responses and a correlation between low serum clusterin during treatment and survival, which was enough to justify two phase 3 trials. Both failed. SYNERGY added custirsen to first-line docetaxel in 1,022 men and found median survival 23.4 against 22.0 months, hazard ratio 0.93 (95 percent confidence interval 0.79 to 1.10, p=0.415). AFFINITY added it to cabazitaxel after docetaxel in 635 men and found 14.1 against 13.4 months, hazard ratio 0.95 (0.80 to 1.12, p=0.53), with no benefit in the prespecified poor-prognosis subgroup either.
OncoGenex, which developed it, is now Achieve Life Sciences and no longer works on cancer. The drug is a clean example of a biomarker association, serum clusterin and survival, that did not survive as a therapeutic target.
Second-generation antisense oligonucleotide that inhibits production of the chaperone protein clusterin.
1.Custirsen slips into a pocket on its target.
Background: ADC sequencing, Antigen escape (antigen loss, lineage switch), BCG-unresponsive, Castration-resistant prostate cancer (CRPC), Circulating tumour DNA (ctDNA). Also on OnCo: Resistance atlas · Lines of therapy.
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Query for this drug: (TITLE:"Custirsen" OR ABSTRACT:"Custirsen" OR TITLE:"OGX-011" OR ABSTRACT:"OGX-011" OR TITLE:"TV-1011" OR ABSTRACT:"TV-1011") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Custirsen, not a curated reading list.
Shares AFFINITY, SYNERGY, Oligonucleotide therapeutics, Castration-resistant prostate cancer (CRPC).
Shares AFFINITY, Castration-resistant prostate cancer (CRPC), Metastatic castration-resistant prostate cancer, Prostate cancer.
Shares Castration-resistant prostate cancer (CRPC), Metastatic castration-resistant prostate cancer, Prostate cancer.
Shares Castration-resistant prostate cancer (CRPC), Metastatic castration-resistant prostate cancer, Prostate cancer.
Shares Metastatic castration-resistant prostate cancer, Prostate cancer.
Shares Castration-resistant prostate cancer (CRPC), Prostate cancer.
Shares Castration-resistant prostate cancer (CRPC), Metastatic castration-resistant prostate cancer, Prostate cancer.