How PF-04518600 works
PF-04518600 targets OX40, a receptor found on the surface of a type of specialized immune cells called memory T-cells that have already been exposed to cancer antigens (substances that trigger an immune response).
The role of OX40 is to promote the division and survival of effector and memory T-cells. It also suppresses the differentiation and activity of another type of T-cell known as regulatory T-cells, which normally function to dampen the immune response to prevent the body from attacking its own tissues. OX40 also regulates the production of cell signaling molecules important for immune response.
PF-04518600 selectively binds to and activates OX40, activating the dormant immune response, which then may help fight cancer cells. The activation of OX40 could also suppress the activity of regulatory-T cells, further increasing the immune response against cancer cells.
PF-04518600 in clinical trials
Preclinical studies have shown that PF-04518600, combined with an immune checkpoint inhibitor or other immunotherapy, may be able to amplify the immune response against tumor cells. So the treatment is being investigated together with several other treatments in Phase 1 and 2 clinical trials.
For example, a Phase 1 dose-escalation trial (NCT02315066) is evaluating PF-04518600 alone or in combination with utomilumab (PF-05082566) to determine the maximum tolerated dose and safety of the treatment in patients with certain types of advanced or metastatic carcinoma.
Preliminary results from 25 patients suggested that PF-04518600 is tolerated up to a dose of 3 mg/kg and showed early anti-tumor activity. The study is currently recruiting patients at more than 30 sites across the U.S., Japan, France, and The Netherlands.
The most common adverse events recorded during the trial were fatigue and decreased appetite.
A Phase 1b/2 study (NCT02554812) of PF-04518600 in combination with Bavencio (avelumab) and utomilumab is ongoing to assess the safety and efficacy of the combination in patients with locally advanced or metastatic solid tumors. The study is currently enrolling patients in the U.S., Canada, Australia, U.K, Japan, France, and The Netherlands.
A randomized Phase 2 trial (NCT03092856) is evaluating PF-04518600 in combination with Inlyta (axitinib) to treat patients with kidney cancer that has spread to other parts of the body. The study aims to enroll 104 patients in the U.S.
Pfizer is also collaborating with the National Cancer Institute to study different treatment combinations of Bavencio with PF-04518600, utomilumab, cisplatin, and radiation therapy in patients with advanced or metastatic solid tumors in a Phase 1b/2 trial (NCT03217747).
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