Patients eligible for the trial include those with advanced or metastatic stages of breast, ovarian, endometrial, or bladder cancers.
B7-H4 belongs to a large family of immune modulators impairing the function of T-cells and anti-tumor immune responses. High levels of the protein in these tumors usually is linked to a poor prognosis.
FPA150 is a therapeutic antibody with a dual mechanism of action. It blocks the B7-H4 inhibitory signals on T-cells, improving immune responses against the tumor, and directly induces the death of B7-H4-positive tumors by recruiting immune cells to their vicinity — a mechanism called antibody-dependent cell-mediated cytotoxicity (ADCC).
The Phase 1 trial will investigate the safety and effectiveness of FPA150 in select solid tumors. In a first part, the trial will dose patients with ascending doses of the antibody to determine the therapy’s maximum tolerated dose. After this initial phase, a dose expansion will be carried out in specific groups of patients according to the levels of expression of B7-H4 in their tumors.
The primary endpoints for the escalation stage include safety and pharmacokinetics profile, i.e., what happens to the therapy in the body, from its entry until excretion. The second phase will assess FPA150’s effectiveness by measuring patients’ objective response rates, i.e., the proportion of patients with a reduction in tumor size.
In an oral presentation, delivered during the European Society for Medical Oncology (ESMO) 2017 Congress, researchers showed that FPA150 had potent ADCC and T-cell checkpoint blockade activity in the laboratory, and was accompanied with significant dose-dependent anti-tumor efficacy animal models.
The presentation was titled “FPA150, a Novel B7-H4 Therapeutic Antibody with Checkpoint Blockade and ADCC Activities.”
“We’re excited to advance into the clinic our targeted, first-in-class B7-H4 antibody, FPA150, which offers a differentiated approach to existing immunotherapies,” Helen Collins, MD, senior vice president and chief medical officer of Five Prime, said in a press release.
“We’re studying FPA150 in patients whose tumors over-express B7-H4 and in which there is high unmet need for immuno-oncology treatments, such as in breast, ovarian and endometrial cancer. We’re hopeful that a targeted therapy such as FPA150 may provide clinical benefit,” she added.