Evaluate Safety and Efficacy of Daily oral Angelica gigas Nakai (AGN)-INM176 in Prostate Patients with Rising Plasma PSA (Phase I/II trial)
Objective
The primary objective of the Phase I stage is to define recommended Phase II dose (RP2D) through 3+3 dose escalation and assess safety of INM176 supplement through 1 cycle (= 4 weeks) for dose-limiting toxicity (DLT) in patients with a history of prostate cancer or low risk disease under active surveillance management.
The primary objective of the Phase II stage is to determine efficacy of INM176 at the RP2D to stabilize or decrease plasma PSA levels after 6 cycles of treatment. The subjects will be post-RP and post-RT patients with rising plasma PSA.
The secondary objectives are several folds:
Perform pharmacokinetics (PK) workup for the first (day 1) and last (day 28) INM176 dose of Cycle 1 and correlate the acute and chronic exposure PK metrics (Cmax, AUC) to safety and PSA efficacy outcomes (when applicable), stratified by CYP 2C19 and 3A4 metabolizer status (Phase I and Phase II).
Measure plasma PSA change trajectory from baseline and after 1 cycle (Phase I and Phase II) and 3 cycles (Phase II) of INM176 supplement at the respective doses as an early efficacy signal.
Immunophenotype blood natural killer (NK) and other cell subsets at baseline and after 1 (Phase I, II), 3 and 6 cycles (Phase II) of INM176 treatment as pharmacodynamic (PD) biomarkers.
Analyze NK functional activity and plasma IL-8 and select cytokines (Phase II) baseline and after 1 (Phase I, II), 3 and 6 cycles (Phase II) of INM176 treatment as PD biomarkers.
Measure male hormones and their binding proteins in plasma (phase II) and correlate to PSA response and PK metrics.
