Evaluation of the safety and efficacy of daily oral Angelica gigas Nakai (AGN)-INM176 in prostate cancer patients with rising plasma PSA (phase I/II trial).

There are currently no FDA approved modalities for intercepting biochemically recurrent prostate cancer after radical prostatectomy (RP) surgery and radiation therapies (RT) to delay or prevent the need for androgen deprivation therapy. Preclinical modeling suggests Angelica gigas Nakai (AGN) root through its signature pyranocoumarins decursin D and decursinol angelate DA and their hepatic metabolite decursinol DOH may meet this unmet clinical need. In a single ascending dose PK study in prostate cancer patients (NCT05375539), we have evaluated the acute safety and shown the exposure PK metrics (C_max and AUC) exhibited a linear dose response to AGN (INM176) supplement in the range of 800 to 2000 mg. The progress strengthens the design and launch of an open label Phase I/II trial to assess the long-term safety and preliminary efficacy of AGN INM176 in intercepting prostate cancer-specific PSA levels with refined inclusion and exclusion criteria. Methods: The ongoing NCT06600698 trial uses a classical Phase I 3+3 dose escalation design to establish the recommended Phase II dose (RP2D). Cohorts of 3 are evaluated for safety of INM176 (800, 1200 and 1600 mg) during a 4-week cycle for dose-limiting toxicities (DLTs). Major inclusion criteria include patients with a history of prostate cancer or those under active surveillance for low-risk disease. Phase II will evaluate the safety and efficacy of INM176 at the RP2D in stabilizing or reducing plasma PSA levels after six cycles of treatment. A special Phase II inclusion criterion is post-RP and post-RT patients experiencing a rise in PSA. In both phases, any patient with warfarin anti-coagulation is excluded due to an adverse herbal-drug interaction raising bleeding risk uncovered in our PK-dose trial. At time of abstract submission, Phase I cohort 1 of three subjects have completed the 800 mg dosing. Enrollment to cohort 2 (1200 mg) began in October 2025. To our knowledge, this is the first known human trial to assess the long-term safety of INM176 at higher than dietary supplement dosage and its interception efficacy for recurrent prostate cancer. The data will inform additional trials in the oncology space and beyond. Grant: MPI R01CA260901 (Lu, Joshi). Clinical trial information: NCT06600698.