How Enadenotucirev works
Enadenotucirev is created by infecting cancer cells with different strains of adenovirus and then selecting the strains that have the most potent and stable tumor-killing activity that are unable to replicate in normal cells.
In that way, when administrated into the bloodstream, enadenotucirev selectively replicates in tumor cells but not in normal cells, promoting an anti-tumor response.
Enadenotucirev has a dual mechanism of action; it is capable of selectively killing tumor cells and at the same time attracting the patients’ immune cells to the site of the tumor to initiate an anti-tumor response.
Enadenotucirev in clinical trials
The mechanism of action, ability to trigger an anti-tumor immune response, and safety of enadenotucirev were assessed in a Phase 1 clinical trial (NCT02053220) in patients with colorectal cancer, non-small cell lung cancer (NSCLC), bladder cancer, and renal cell carcinoma.
The results of the study, Phase 1 study of intravenous administration of the chimeric adenovirus enadenotucirev in patients undergoing primary tumor resection, were published in the Journal for ImmunoTherapy of Cancer. It showed that enadenotucirev was present in most tumor samples with little or no activity in normal tissue. Moreover, the researchers observed that enadenotucirev led to an immune response in 80 percent of tested tumor samples. No treatment-associated serious adverse events were recorded.
The safety, tolerability, and effectiveness of enadenotucirev also are being evaluated in another Phase 1/2 trial (NCT02028442) called EVOLVE (Evaluating Oncolytic Vaccine Efficacy). The aim of the Phase 1 portion of the trial is to determine the maximum tolerated dose of enadenotucirev, given in a single cycle. The Phase 2 portion was designed to evaluate the effect of two repeat-cycle schedules of the vaccine, at the maximum tolerated dose.
According to the first results of the trial presented at the ESMO Immuno-Oncology Congress in 2017, investigators were able to determine the maximum tolerated dose of the treatment based on adverse events occurring on day one of the first cycle. According to the investigators, manipulation of dosing regimens may allow the administration of higher doses of enadenotucirev, or more doses per cycle, to increase and optimize its effectiveness. The trial, which is being performed in Belgium and Spain, is ongoing, but no longer recruiting patients.
PsiOxus Therapeutics also is evaluating enadenotucirev in two additional studies.
The OCTAVE study, a phase 1/2 non-randomized multicenter trial (NCT02028117) is evaluating enadenotucirev administered in the abdominal cavity of patients with platinum-resistant epithelial ovarian cancer. The Phase 1 portion of the study was designed to determine the maximum tolerated dose and to assess the safety, tolerability, and pharmacokinetics (movement inside the body) of the treatment, either alone or in combination with Taxol (paclitaxel). In the Phase 2 portion, investigators will determine whether enadenotucirev injected in the abdominal cavity has a risk-benefit profile that supports further investigation in the treatment of patients with platinum-resistant epithelial ovarian cancer.
PsiOxus Therapeutics presented the first results from seven patients enrolled in the trial, at the American Society of Clinical Oncology (ASCO) 2016 annual meeting. Researchers verified that enadenotucirev was well-tolerated, supporting its testing in combination with Taxol.
The trial was expected to enroll up to 35 participants in Spain and the U.K. and was planned to be completed in January 2018. However, it is still recruiting patients.
A Phase 1 clinical trial (NCT02636036) called SPICE (Study of PD-1 Inhibition in Combination with Enadenotucirev), which is a collaboration between PsiOxus Therapeutics and Bristol-Myers Squibb, will evaluate the maximum tolerated dose, safety, tolerability, and effectiveness of enadenotucirev in combination with Opvido (nivolumab) in patients with metastatic or advanced epithelial tumors.
The study is recruiting up to 30 participants at four U.S. sites and is expected to be completed in June 2019.
The most commonly reported adverse effects caused by enadenotucirev were fever, weakness, abdominal pain, and an abnormally low concentration of some types of white blood cells.
In 2015, the European Medicines Agency’s (EMA) granted enadenotucirev orphan drug status for the treatment of epithelial ovarian cancer in combination with Taxol. (Investigational therapies for rare, or orphan, diseases with few or no approved treatments are designated orphan drugs to help speed their development).
Immuno-Oncology News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.