How APVO414 works
APVO414 is a bispecific antibody, a molecule that is able to simultaneously bind to two proteins: one on the surface of malignant prostate cancer cells, and the other on the surface of certain immune system tumor-killing cells called a T-cells.
The protein on the surface of prostate cancer cells is called prostate specific membrane antigen (PSMA), and the protein on the surface of T-cells is called CD3. The binding of APVO414 to both these proteins simultaneously recruits T-cells to the tumor site, allowing them to destroy prostate cancer cells containing PSMA.
APVO414 in clinical trials
In preclinical studies, APVO414 showed the ability to stimulate the proliferation of T-cells and increase their anti-cancer killing ability. These first results were presented at the American Association for Cancer Research (AACR) 2016 Annual Meeting, and published in the Journal of Molecular and Cellular Biology.
Aptevo then started a Phase 1 clinical trial (NCT02262910) to investigate increasing doses of APVO414 in patients with castrate-resistant prostate cancer. The trial, which is still recruiting patients in the U.S and Australia, aims to evaluate the safety, tolerability, and effectiveness of APVO414.
Preliminary results announced by the company pointed to the preferred administration method of APVO414 being continuous infusion instead of weekly infusion, because it led to fewer antibodies being produced against the treatment. These antibodies, called anti-drug antibodies, neutralize the therapy’s effectiveness. In other words, these results showed that the mode of administration of APVO414 was important for its effectiveness.
Investigators are now testing increasing doses of APVO414 to determine its maximum tolerated dose (MTD). Once the MTD is identified, the trial’s second stage will begin and evaluate the effectiveness of APVO414 in two groups of patients: those who have and those who have not received chemotherapy previously. The ability of APVO414 to trigger an immune response and its effect on the body will also be investigated.
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