The study will be conducted in 2 Stages. The primary objective of Stage 1 of the study is
to identify the maximum tolerated dose (MTD) of ES414 administered intravenously to
patients with mCRPC. Secondary objectives are to evaluate the tolerability,
pharmacokinetics (PK), pharmacodynamics (PD), immunogenicity, cytokine response, and
clinical activity of ES414.
The primary objective of Stage 2 of the study is to evaluate the clinical activity of
ES414 in patients that have or have not received prior chemotherapy. Secondary objectives
are to further characterize the safety profile, PK, PD, and immunogenicity of ES414.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02262910.
Stage 1 - Dose Escalation: The dose escalation stage of the study will test weekly doses
of 0.2 mcg/kg to 300 mcg/kg over 9 dose levels (cohorts). Cohorts 1 to 3 consist of
single patients and Cohorts 4 - 9 will consist of a minimum of 3 patients; an additional
3 patients may be added to the cohort if adverse events possibly related to ES414 or
dose-limiting toxicities (DLT) occur. The next dose cohort will only enroll after the
patient(s) in the current dose cohort have completed the first cycle of dosing (4 weeks)
with no significant adverse events or DLTs. Six patients will be enrolled at the maximum
tolerated dose (MTD) and this dose will be used for Stage 2.
Stage 2 - Expansion: The continuous intravenous infusion MTD dose regimen will be further
examined in 2 expansion cohorts; the first cohort are patients that have received prior
chemotherapy, such as docetaxel for mCRPC, and the second cohort are those that have not
received prior chemotherapy for mCRPC. Serum samples will be collected for serial PK
assessment for ES414 drug levels and antibody formation. Response will be assessed every
2 months during the first 6 months of treatment and then every 3 months until progression
of mCRPC, intolerable side effects, or withdrawal of consent.
Lead OrganizationAptevo Therapeutics
