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The peptide cancer vaccine onilcamotide failed to show superiority over placebo in terms of preventing progression in patients with prostate cancer and biochemical recurrence following curative-intent therapy, missing the primary end point of the phase 2b BRaVac trial.
The peptide cancer vaccine onilcamotide (RV001) failed to show superiority over placebo in terms of preventing progression in patients with prostate cancer and biochemical recurrence following curative-intent therapy, missing the primary end point of the phase 2b BRaVac trial (NCT04114825).1
Interim safety reviews have been performed, and no unexpected toxicities have been observed with the agent. However, primary efficacy results did not suggest any significant improvement in outcomes for the patients analyzed.
RhoVac AB, the drug developer, shared plans to perform further analyses of the results and to develop a cost minimization contingency plan. However, the primary outcome analysis of data from this study alone do not support a license or acquisition deal, according to the company.
“Even though we know that benchmarks state that the probability of success for a phase 2 project in oncology is less than 50% and that clinical development is always a calculated risk, we are surprised and deeply saddened to find that BRaVac failed to meet its primary end point,” Anders Månsson, chief executive officer of RhoVac, stated in a press release. “We will immediately minimize expenditure, while further assessing the data, with the aim of coming up with firm recommendations on how to proceed, and to communicate this end [of] June.”
Onilcamotide is presented to the immune system as an antigen that stimulates T cells to identify and eliminate metastatic or metastatic potential cells that carry RhoC.2 Historically, cancer vaccines have not demonstrated acceptable efficacy in the treatment of patients with solid tumors. This agent differs in that it only targets metastatic cancer cells and metastases in early formation.
The product is administered to patients via a subcutaneous injection. Dendritic cells capture and absorb the product and subsequent transform into antigen-presenting cells. These cells then interact with naïve T cells and convert them into CD8-positive T cells. CD4-positive T cells are also formed, and they serve to strengthen the ability of the immune system to combat the cancer.
The double-blind, placebo-controlled, phase 2b trial enrolled patients with an earlier histologic diagnosis of prostatic adenocarcinoma who experienced biochemical recurrence within 3 years of radical prostatectomy or definitive radiotherapy and no distant metastasis.3 These patients had an ECOG performance status of 0 to 2, a creatinine level of up to 1.5 x upper limit of normal (ULN), and alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels of up to 2.5 x ULN.
If patients were receiving androgen deprivation therapy (ADT) or were eligible to receive immediate ADT, if they were planned to receive salvage therapy with radiation treatment or radical prostatectomy, if they had a castrate level of serum testosterone of less than 50 ng/dL at screening, or if they had a prostate-specific antigen (PSA) of greater than 10 ng/mL, they were excluded.
The trial planned to enroll 180 patients. Those in the investigative arm received a total of 12 subcutaneous vaccinations of the vaccine. The first 6 vaccinations occurred during the priming period and were given every 2 weeks, and the subsequent 5 vaccinations were given with 4 weeks between vaccinations as part of the maintenance period. The last, and twelfth, vaccination was slated to be given 6 months after the eleventh vaccination.
The primary end point was time to PSA progression, and secondary end points included safety, time to initiation of subsequent antineoplastic therapy, proportion of patients with a PSA response from baseline, and disease-free survival.
Preclinical data indicated that MHC-II receptors are found in several forms of cancer cells, and that RhoC is co-located with these receptors on the cell surface. Findings from a preclinical study collaboration done with faculty within St. Johns National Academy of Heath Sciences, CBCI, showed that onilcamotide is tissue agnostic, with the potential to be utilized across cancer types.4
“We are very excited about these findings that coincide with previous preclinical findings suggesting a potential broad use of onilcamotide in cancer, provided we also get a first clinical proof of concept for its use in prostate cancer,” Månsson had previously stated.
In November 2020, the FDA granted a fast track designation to onilcamotide for this patient population.