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Custirsen (OGX-011)

Custirsen: Designed to Inhibit the Cytoprotective Chaperone Protein Clusterin

Custirsen is an experimental drug that is designed to block the production of the protein clusterin, which may play a fundamental role in cancer cell survival and treatment resistance. Clusterin is upregulated in tumor cells in response to treatment interventions such as chemotherapy, hormone ablation and radiation therapy and has been found to be overexpressed in a number of cancers, including prostate, lung, breast and bladder. Increased clusterin production has been linked to faster rates of cancer progression, treatment resistance and shorter survival duration. By inhibiting clusterin, custirsen is designed to alter tumor dynamics, slowing tumor growth and resistance to partner treatments, so that the benefits of therapy, including survival, may be extended.

As part of Phase 1 and Phase 2 clinical trials, custirsen was administered to 294 patients with various types of cancer. The majority of adverse events were mild. The most common adverse events associated with custirsen consisted of flu-like symptoms. The most common serious adverse events (SAE) associated with custirsen were febrile neutropenia, fever, pleural effusion, and dyspnea. Each SAE event was observed in approximately 2%-4% of patients.


Research shows that clusterin contributes to cancer’s ability to resist apoptosis by:

  • Inhibiting proapoptotic signaling through interaction with surface proteins (eg, receptors) on stressed cells
  • Inhibiting the proapoptotic protein Bax to prevent its activation of the intrinsic pathway through the mitochondria
  • Promoting cell survival by enhancing NF-_B transcriptional activity
  • Inhibiting endoplasmic reticulum stress and the aggregation of proteins to maintain protein homeostasis

Clinical Trial Results

  • Custirsen has been administered to nearly 300 patients with various types of cancer in Phase 1 and Phase 2 clinical trials.
  • A broad range of preclinical studies show that custirsen decreases clusterin levels and sensitizes tumor cells to standard chemotherapeutic drugs.
  • Custirsen’s ability to enhance the effects of standard therapies has been evaluated in five Phase 2 clinical trials.  The Phase 2 results in prostate cancer suggest there may be an overall survival benefit as well as an improvement in durable pain palliation in prostate cancer. Phase 2 results in lung cancer suggest survival outcomes compared favorably with previously published data of similar regimens.

Learn more about Phase 1 Clinical Trial Results.

Learn more about Phase 2 Clinical Trial Results.

Clinical Development Program

AFFINITY: Phase 3 Trial of Custirsen in Second-Line Metastatic Castrate-Resistant Prostate Cancer (CRPC)

AFFINITY is a company-sponsored, randomized Phase 3 trial evaluating whether custirsen, when combined with the second-line chemotherapy, Jevtana® (cabazitaxel), has the potential to improve survival outcomes for metastatic CRPC patients who have progressed following treatment with docetaxel. Patients will be randomly selected to receive Jevtana plus prednisone with or without custirsen therapy, and are eligible for the trial regardless of prior therapy with androgen targeting treatments such as Zytiga® (abiraterone acetate) or Xtandi® (enzalutamide).

The trial will enroll approximately 630 men with metastatic CRPC and is being conducted throughout North America, Europe, Russia and Australia.

NOW ENROLLING: Learn more about AFFINITY

Phase 3 Clinical Trial in Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC)

ENSPIRIT is a company-sponsored Phase 3 trial evaluating the potential of custirsen to improve survival outcomes in patients with advanced or metastatic NSCLC who have progressed after initial chemotherapy treatment has failed. Patients will be randomly selected to receive a second-line standard of care, docetaxel treatment, with or without custirsen therapy.

The trial will enroll approximately 1,100 patients with advanced or metastatic NSCLC and is being conducted internationally.

NOW ENROLLING: Learn more about ENSPIRIT

Phase 3 Clinical Trial in First-Line Metastatic Castrate-Resistant Prostate Cancer (CRPC)

SYNERGY is a company-sponsored, randomized Phase 3 trial evaluating the ability of custirsen to improve survival when added to first-line chemotherapy standard of care, docetaxel treatment. Patients will be randomly selected to receive the standard of care, with or without custirsen therapy.

The trial has enrolled approximately 1,000 men with metastatic CRPC at approximately 123 cancer centers throughout North America and Europe.

  • SPA completed with the FDA
  • Received Fast Track Designation
  • FDA stated that an application supported primarily by the results of SYNERGY alone would be acceptable for submission

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