Abstract 1386P
Background
PRL-02 is a long-acting IM depot injection of abiraterone decanoate, a novel prodrug of abiraterone. In non-clinical models PRL-02 provides high and durable concentrations of prodrug and abiraterone in target tissues and organs (including adrenal, lymph and bone). Single doses of PRL-02 markedly depressed testosterone (T) through 14 weeks in a castrate monkey model to levels comparable to clinical results with oral abiraterone acetate (AA) but with lower and less variable plasma exposures. The totality of nonclinical data study results suggests that PRL-02 has the potential for a superior therapeutic index and safety profile compared to oral AA.
Methods
The phase 1 is a standard 3+3 dose escalation design (DLT period = 28 days) intended to identify a RP2D with adequate suppression of T ( < 1ng/dL) for a minimum of 12 weeks. PRL-02 is administered as an IM injection every 84 days. Patients with biochemical relapse, mCSPC, or mCRPC and had a prior orchiectomy or ongoing GnRH analogue therapy for at least 3 months and a screening T level 2 - 50 ng/dL are included. Exclusions include prior treatment with a CYP17 inhibitor, concurrent treatment with an AR blocking agent.
Results
At the data cut off of April 18 2022, 15 patients with a median age 68 (4 mCRPC, 11mCSPC) were treated at 5 dose levels (180mg, 360mg, 720mg, 1260mg, 1800mg). T suppression, without changes in progesterone or cortisol due to inhibition of CYP17 hydroxylase, was observed in all patients. At 720mg and 1260mg the median baseline T level was 7.63ng/dL. All but two patients in whom data is available, achieved either a 90% reduction in T or values ≤ 1ng/dL at cycle 1 day 28. Data is immature at 1800mg and at later timepoints. At 720mg and 1260mg PSA responses were observed in all 5 patients in whom post baseline PSA is available. No patients have progressed while on treatment. PRL-02 was well tolerated with no DLTs, no treatment related SAEs and no AEs related to PRL-02 with severity greater than CTCAE G2. Two CTCAE G2 events were considered possibly related to study drug: fatigue, loss of appetite.
Conclusions
PRL-02 was well tolerated. Dose dependent T suppression associated with clinical benefit (PSA response / radiographic improvement) was observed. The study continues.
Clinical trial identification
NCT04729114.
Editorial acknowledgement
Legal entity responsible for the study
Propella Therapeutics, Inc.
Funding
Propella Therapeutics, Inc.
Disclosure
J.L. Bailen MD: Financial Interests, Institutional, Invited Speaker: Pfizer, Janssen, Bayer. N.D. Shore: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Boston Scientific, Clovis Oncology, Cold Genesys, Dendreon, Exact Imaging, Exact Sciences, FerGene, Foundation Medicine, Genesis Care Us, Invitae, Janssen, MDxhealth, Merck, Myovant, Myriad, Nymox, Pacific Edge, Pfizer, Phosphorous, Propella, PreView, Sanofi Genzyme, Speciality Networks, Sesen Bio, Tolmar, UroGen. R.F. Tutrone: Financial Interests, Personal, Invited Speaker: Myovant, Pfizer, Astellas; Financial Interests, Personal, Advisory Board: Exosome Diagnostics, Bayer, Janssen, Nymox; Financial Interests, Personal, Stocks/Shares: Nymox, Veru, Myovant; Financial Interests, Institutional, Invited Speaker: Exosome, Propella, Point Biopharma, Bayer, Veru, Astellas, Merck, Janssen, Myovant. J. Walling: Financial Interests, Institutional, Other, Consulting work: Aduro, Ambagon Therapeutics, Aminex Therapeutics, Arch Oncology, Aro Biotherapeutics, CytomX Therapeutics, Flag Therapeutics, Harpoon Therapeutics, January Therapeutics, Janux Therapeutics, Myovant, Nurix Biotech, Nuvation Bio, Opna, Orbus Therapeutics, Oryzon Genomics, Propella Therapeutics, Proximagen Neurosciences, Que Oncology, Rhizen Pharmaceuticals, Sesen Bio, Shape Therapeutics, Stealth Biotherapeutics, TRex Bio, Upsher-Smith; Financial Interests, Institutional, Other, consulting work: Plexxikon; Financial Interests, Institutional, Officer, CMO: Arch Oncology, Nurix, Plexxikon. L. Peterson: Financial Interests, Personal, Full or part-time Employment: Propella Therapeutics; Financial Interests, Personal, Stocks/Shares: Propella Therapeutics; Non-Financial Interests, Leadership Role: Propella Therapeutics; Non-Financial Interests, Personal, Proprietary Information: Propella Therapeutics. R. Schotzinger: Financial Interests, Personal, Other, Consultant and Board Member: Propella Therapeutics; Financial Interests, Personal, Invited Speaker: Propella Therapeutics; Financial Interests, Personal, Stocks/Shares: Propella Therapeutics. W.R. Moore: Financial Interests, Personal, Officer, I am the CEO and a Board Director for Propella Therapeutics: Propella Therapeutics; Financial Interests, Personal, Stocks/Shares: Propella Therapeutics. All other authors have declared no conflicts of interest.