A phase II study combining ipilimumab and degarelix with or without radical prostatectomy (RP) in men with newly diagnosed metastatic noncastration prostate cancer (mNCPC) or biochemically recurrent (BR) NCPC.

Abstract

203 Background: Androgen deprivation therapy (ADT) does not completely eliminate disease in mNCPC or BRPC. We explored a multimodality treatment (tx) approach combining ADT with ipilimumab (ipi) with the aim of achieving no evidence of disease or complete elimination of disease, given the potential for cure seen with immunotherapy. Methods: Cohort A (Coh A) enrolled men with ≤ 10 bone metastases treated with induction of degarelix (deg) and ipi prior to RP and subsequent ipi q3 weeks x 3 and 8 months (mos) total of deg. Cohort B (Coh B) opened later and enrolled men with BRNCPC after RP with a doubling time ≤ 12 mos, and received ipi q3 weeks x 4 and 8 mos of deg. The primary endpoint was an undetectable PSA (<0.05) at 12 and 20 mos with non-castrate testosterone. Results: 16 pts (7 Coh A; 9 Coh B) were treated. No Coh A pts experienced immune related toxicities (irAE) that delayed surgery. 4/7 (57%) Coh A pts came off study for irAE, 1 (14%) for insurance reasons, and 2 (29%) completed all protocol requirements. In Coh B 6/9 (67%) pts have completed tx and entered follow-up. Conclusions: A combined modality approach with ipi 10mg/kg, ADT, and RP in mNCPC was associated with limiting toxicities, however 3mg/kg was better tolerated and more feasible in a BRNCPC cohort. One pt in Coh A (14%) had an undetectable PSA with testosterone recovery while evaluation of efficacy for Coh B is ongoing. The role for RP and other immunotherapeutic approaches in NCPC remain viable interests to the field. Clinical trial information: NCT02020070. [Table: see text]

Immune Checkpoint Inhibitors for Genitourinary Cancers: Treatment Indications, Investigational Approaches and Biomarkers

“…Multiple phase 1 and phase 2 trials are evaluating ICI in combination with treatments such as abiraterone and cabozantinib [NCT04477512], radiation therapy [NCT04262154, NCT03795207] and an experimental IL-8 directed monoclonal antibody [NCT03689699]. In addition, perioperative ipilimumab in combination with castration prior to radical prostatectomy has demonstrated feasibility with longer follow-up ongoing [128].…”

Immunotherapy in the Treatment of Localized Genitourinary Cancers

“…Ka et al performed a proof-of-concept phase 1 trial looking at the effect of androgen deprivation therapy and ipilimumab in patients with biochemically recurrent prostate cancer postprostatectomy or with localized prostate cancer and oligometastases who underwent prostatectomy with the end point of an undetectable PSA level (<0.05 ng/mL) at 12 and 20 months with a noncastrate level of testosterone. Although safe and feasible, there was no significant effect on delay to PSA relapse.…”

Genetic Aberrations of DNA Repair Pathways in Prostate Cancer: Translation to the Clinic

“…Multiple phase I and phase II trials are evaluating immune checkpoint inhibitors in combination with treatments such as abiraterone and cabozantinib [NCT04477512], radiation therapy [NCT04262154, NCT03795207], and an experimental IL-8 directed monoclonal antibody [NCT03689699]. In addition, perioperative ipilimumab in combination with castration prior to radical prostatectomy has demonstrated feasibility with longer follow-up ongoing [ 65 ].…”