RGX is an investigational, non-peptide gonadotropin-releasing hormone (GnRH) antagonist of the human GnRH receptor (IC50 0.12 nM). This open label, parallel group study evaluated the testosterone (T)-lowering efficacy, safety and PK of RGX vs the injectable peptide GnRH antagonist DGX in pts with PC.
Men aged ≥18 y with intermediate risk localized PC appropriate for EBRT and 6 mos ADT, with baseline T >150.0 ng/dL, and prostate specific antigen (PSA) >2.0 ng/mL received oral RGX 320.0 mg on d 1 then 120.0 mg once daily (QD) or DGX 240.0 mg on d 1 then 80.0 mg SC Q4W for 24 wks. The primary endpoint was % of pts with castrate T levels
At data cut-off (March 2016) after 24wks, sustained castration rates were 95% in RGX treated pts (N = 65; median age 71.0 y) vs 89% with DGX (N = 38; 70.5 y). Median T with RGX vs DGX were 53.0 ng/dL (23.9–306.8) vs 49.0 ng/dL (23.0–223.9) after 24 h and 7.8 ng/dL (2.9–53.0) vs 10.1 ng/dL (3.2–236.8) after 12 wks. Prostate size reductions at 8-12 wks were similar in both arms, as were PSA change from baseline values (median -91.2% vs -88.6%). (Table.) Sexual activity per PR-25 was partially recovered after stop of treatment in both arms and further QoL analysis is ongoing. No pts discontinued due to Rx-related adverse events, most common were (RGX/DGX): hot flush (57/61%), fatigue (26/16%), and diarrhea (18/13%).
|Median (range)||Baseline||After 24 Wks||4 Wks Post-Rx Discontinuation||8 Wks Post-Rx Discontinuation||12 Wks Post-Rx Discontinuation|
|RGX LH, IU/L||4.7 (0.8–32.2)||0.1 (0.1–3.9)||3.1 (0.2–15.7)||8.3 (0.1–32.4)||10.7 (0.1–38.7)|
|DGX LH, IU/L||4.8 (1.3–42.0)||0.1 (0.1–3.7)||0.2 (0.1–2.8)||0.5 (0.1–7.7)||1.4 (0.1–15.7)|
|RGX T, ng/dL||355.9 (149.0–1290.0)||8.1 (3.2–125.0)||94.0 (2.9–818.8)||238.4 (10.1–929.8)||257.0 (9.5–858.8)|
|DGX T, ng/dL||404.0 (138.0–937.8)||8.9 (2.9–272.8)||9.7 (2.9–225.0)||16.1 (3.2–263.0)||30.0 (3.7–378.8)|
|RGX PSA, ug/L||7.3 (2.6–31.5)||0.1 (0.1–1.6)||0.1 (0.1–1.5)||0.19 (0.1–3.2)||0.19 (0.1–2.3)|
|DGX PSA, ug/L||7.3 (2.5–88.9)||0.1 (0.1–1.8)||0.1 (0.1–2.1)||0.1 (0.1–2.2)||0.07 (0.1–2.0)|
Oral RGX and injectable DGX have similar T-lowering and clinical efficacy. Recovery of T levels occur sooner in RGX arm vs DGX. Oral RGX may be a potentially advantageous option for GnRH antagonist therapy and will be further studied vs depot GnRH agonists in phase 3.
Clinical trial identification
Legal entity responsible for the study
Millennium Pharmaceuticals, Inc.
Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited
D.P. Dearnaley: Advisory board (Millennium Pharmaceuticals, Inc., Janssen Pharma).
D.R. Saltzstein: Consultancy/advisory role (Astellas, Bayer, Janssen, Tolmar), Investigator/scientific study/trial (Astellas, Neogenomics, Oncocyte, Tokai), and Meeting participant/lecturer (Astellas, Bayer, Janssen); Research funding (Millennium Pharmaceuticals, Inc., Tokai).
L. Karsh: Consultancy/advisory role (AbbVie, Amgen, Argos, Astellas, Medivation, Bayer, BNIT, Dendreon, Heat Biologics, Janssen, Myriad, Sanofi, Spectum, Swan Valley Medical, Tolmar); Speaker (Astellas/Medivation, Bayer, Dendreon, Janssen); and PI Clinical Trials (Argos, Astellas, Medivation, Augmenix, Auxilium, BNIT, Dendreon, FKD Therapies, Genome DX Biosciences, Genomic Health Inc., Heat Biologics, Janssen, MDx Health, Pfizer, Spectrum,Takeda).
B.A. Mehlhaff: Consultant (AbbVie, Amgen, Astellas, Medivation, Bayer, Dendreon, Janssen, Myriad; Speaker (AbbVie, Amgen, Astellas/Medivation, Bayer, Dendreon, Janssen); PI Clinical Trials (Astellas, Medivation, Augmenix, Bayer, Dendreon, Genomic Health Inc., Janssen, MDx Health, Millennium Pharmaceuticals, Takeda, Tokai).
C. Pieczonka: Research funding (Millennium Pharmaceuticals, Inc., Janssen, Dendreon, Astellas, Bayer); Consultancy/advisory role (Janssen, Bayer); Honoraria and Speakers' Bureau (Janssen, Dendreon, Astellas, Bayer).
J.L. Bailen: Research funding (Astellas, Bayer, Dendreon, Janssen, Medivation, Millennium Pharmaceuticals, Inc.) and Honoraria, Consultancy/advisory role, and Speakers' Bureau (Astellas, Auxilium, Bayer, Dendreon, Janssen, Sanofi).
D.B. MacLean, S. Sankoh, H.M. Faessel and H.M. Lin: Employment (Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited)
N.D. Shore: Consultancy/advisory role (Astellas, Bayer, Dendreon, Ferring, Janssen, Medivation, Sanofi); Research funding and Consultancy/advisory role (Millennium Pharmaceuticals, Inc.).
All other authors have declared no conflicts of interest.