A combination of Vaccitech’s experimental vaccine VTP-800 and Opdivo (nivolumab) appears to be a safe and potentially effective treatment for men with metastatic castration resistant prostate cancer (mCRPC), according to early data from a Phase 2a part of clinical trial.
The open-label study (NCT03815942), called ADVANCE, may still be recruiting up to 36 patients in the U.K. It is sponsored and being conducted by the University of Oxford, and is co-funded by Vaccitech and the FP7 programme of the European Commission.
The trial’s main goal is to assess the safety and efficacy of VTP-800 when used in combination with Bristol-Myers Squibb‘s Opdivo at reducing blood levels of prostate-specific antigen (PSA) in men with intermediate risk or advanced prostate cancer.
VTP-800 is a potential anti-cancer vaccine designed to prime the immune system to target and kill cancer cells. Specifically, it is intended to make the immune system kill cells with a protein called 5T4 on their surface. The vaccine is made of two engineered and harmless viruses, and designed to produce 5T4 in the body to help immune system to target this protein.
Opdivo, a type of therapy known as checkpoint inhibitor, works by blocking the binding of the PD-1 protein on immune cells with PD-L1 on cancer cells, which is a mechanism used by tumors to evade immune attack.
Those with advanced mCRPC participating in ADVANCE are being given two cycles of VTP-800 every four weeks, along with an intravenous infusion (directly into the bloodstream) of Opdivo on weeks 4, 8 and 12.
Interim results from ADVANCE, announced in a release, covering 23 mCRPC patients given VTP-800 in combination with Opdivo, showed five (22%) had more than a 50% reduction in their blood PSA levels from those recorded at the study’s beginning (baseline levels).
These findings compare favorably, the release stated, to the 9% treatment response rate reported in KEYNOTE-199, a Phase 2 trial (NCT02787005) that assessed the safety and effectiveness of the anti-PD-1 agent Keytruda (pembrolizumab) in 243 men with mCRPC and similar PSA baseline levels (median of 88 ng/ml).
Results also found that four of the five men responding to treatment in ADVANCE (17.4% of the total group) maintained this response over three weeks, and one treated patient had a PSA level of 0 at week 24 (six months after treatment start).
This study, which opened in December 2018, is expected to finish with primary data collection in December of this year.
”We have seen promising clinical activity of VTP-800 in conjunction with an anti-PD-1, including responses in patients with advanced hormone resistant prostate cancer that are resistant to standard treatments,” Mark Tuthill, the trial’s chief investigator, said in the release. “These encouraging data will hopefully lead to the initiation of a larger phase 2 clinical trial in patients with advanced prostate cancer.”
Initial safety data are comparable to those seen with an anti-PD-1 therapy alone. No serious adverse events were deemed related to VTP-800.
“We are encouraged by these data … and look forward to continuing to work with Oxford University to explore options for future clinical studies to evaluate the added patient benefit VTP-800 can provide when combined with checkpoint inhibitors,” said Bill Enright, CEO of Vaccitech.
A full analysis of trial results is pending, and the company said it plans to present ADVANCE data a medical conference later this year.