Fleming, Mark T.

e17064 Background: Analyses of clinical trials data suggest thatBlack men have equal or even improved overall survival (OS) with certain treatments for mCRPC compared with other races. Moreover, retrospective analysis of the PROCEED registry indicated that Black men who received Sip-T, an autologous cellular immunotherapy, had longer survival compared with other men with mCRPC. The Abi Race and PANTHER clinical trials prospectively assessed the effect of ARPIs on clinical outcomes among Black and White patient (pt) cohorts, and included pts who had received Sip-T either prior to or during study. We combined data from Abi Race and PANTHER to investigate associations between OS, Sip-T and race. Methods: Data from the Abi Race (N=100) and PANTHER (N=93) studies were retrospectively pooled for this analysis. Propensity scores for Sip-T treatment were calculated based on Karnofsky performance status, race, Gleason score, and study. Kaplan-Meier estimates for OS, with and without inverse propensity score weighting, were generated and stratified by Sip-T use. This analysis was stratified by race to examine whether the relationship between Sip-T use and OS differed by race. Results: Of the 93 Black pts and 100 White patients included from both studies, 123 patients did not receive Sip-T, while 70 patients did (60 before study, 10 on study). Pts who received Sip-T had a median OS (mOS) of 44 months (95% Confidence Interval (CI) 39, NR) compared to 36 months (95% CI 31, 48) for those who did not. Weighted by propensity scores, Black men who received Sip-T had a mOS of 72 months (95% CI 43, NR), while those who did not had a mOS of 38 months (95% CI 30, NR). Among White men, patients who received Sip-T had a mOS of 39 months (95% CI 30, NR), while those who did not had a mOS of 32 months (95% CI 29, 48) (see Table). Conclusions: Our findings from an investigator-led retrospective analysis independent of sponsors provide independent clinical trial support of prior retrospective findings that suggest Black men with mCRPC who receive Sip-T may have a greater OS than White men. While our analysis controlled for factors that may influence the use of Sip-T, it is limited by potential unmeasured confounders or timing of Sip-T. Further, adequately powered prospective trials specifically evaluating outcomes with Sip-T by race in earlier clinical settings are needed. Drug support and funding for Abi Race and PANTHER were provided by Janssen Scientific Affairs, LLC. Death counts and median overall survival (mOS) in months by race and Sipuleucel-T use. Black Men White Men Sipuleucel-T use Deaths / Total N No 36 / 64 38 / 59 Yes 12 / 29 24 / 41 Unweighted mOS (95% CI) No 36 (29, NR) 32 (29, 48) Yes 72 (43, NR) 39 (31, NR) Weighted mOS (95% CI) No 38 (30, NR) 32 (29, 48) Yes 72 (43, NR) 39 (30, NR) NR = not reached, mOS = median overall survival, CI = confidence interval.

5003 Background: [177Lu]Lu-PSMA-617 (177Lu-PSMA-617) prolonged radiographic progression-free survival vs change of androgen receptor pathway inhibitor (ARPI) in taxane-naïve patients with metastatic castration-resistant prostate cancer (mCRPC) in PSMAfore (NCT04689828). We now present health-related quality of life (HRQoL) and pain outcomes at second interim analysis. Methods: Eligible patients had mCRPC, were candidates for change of ARPI after progression on one prior ARPI, and had ≥1 PSMA-positive and no exclusionary PSMA-negative metastatic lesions by [68Ga]Ga-PSMA-11 PET/CT. Ineligible patients were candidates for PARP inhibition or had received prior systemic radiotherapy, immunotherapy or chemotherapy. Patients were randomized 1:1 to open-label 177Lu-PSMA-617 (7.4 GBq/6 weeks; 6 cycles) or ARPI change (abiraterone/enzalutamide). Patients with confirmed radiographic progression on ARPI change could cross over to 177Lu-PSMA-617. Secondary endpoints included time to worsening (TTW) in self-reported HRQoL (FACT-P, EQ-5D-5L) and pain (BPI-SF), defined as a composite of score worsening (prespecified thresholds), clinical progression (including new anti-cancer treatment) or death. Post hoc analyses of TTW in FACT-P and BPI-SF excluded clinical progression and death. The study was not powered for these endpoints and type I error was not controlled. Results: We randomized 468 patients (234/arm) with a median age of 72 years (range, 43–94). Median duration of exposure was 8.4 months for 177Lu-PSMA-617 and 6.5 months for ARPI change. 177Lu-PSMA-617 delayed TTW in FACT-P, EQ-5D-5L and BPI-SF scales and subscales vs ARPI change (Table). Results were similar in non-composite analyses. Incidence of grade ≥3 adverse events (AEs), serious AEs and AEs leading to discontinuation for 177Lu-PSMA-617 and ARPI change were 34% vs 44%, 20% vs 28% and 5.7% vs 5.2%, respectively. Conclusions: 177Lu-PSMA-617 delayed TTW in self-reported pain and HRQoL vs change of ARPI in taxane-naïve patients with PSMA-positive mCRPC. Clinical trial information: NCT04689828 . [Table: see text]

AbstractBackgroundProstate‐specific membrane antigen (PSMA) is a well‐established therapeutic and diagnostic target overexpressed in both primary and metastatic prostate cancers. PSMA antibody‐drug conjugate (PSMA ADC) is a fully human immunoglobulin G1 anti‐PSMA monoclonal antibody conjugated to monomethylauristatin E, which binds to PSMA‐positive cells and induces cytotoxicity. In a phase 1 study, PSMA ADC was well tolerated and demonstrated activity as measured by reductions in serum prostate‐specific antigen (PSA) and circulating tumor cells (CTCs). To further assess PSMA ADC, we conducted a phase 2 trial in metastatic castration‐resistant prostate cancer (mCRPC) subjects who progressed following abiraterone/enzalutamide (abi/enz) therapy.MethodsA total of 119 (84 chemotherapy‐experienced and 35 chemotherapy‐naïve) subjects were administered PSMA ADC 2.5 or 2.3 mg/kg IV q3w for up to eight cycles. Antitumor activity (best percentage declines in PSA and CTCs from baseline and tumor responses through radiological imaging), exploratory biomarkers, and safety (monitoring of adverse events [AEs], clinical laboratory tests, and Eastern Cooperative Oncology Group performance status) were assessed.ResultsPSA declines ≥50% occurred in 14% of all treated (n = 113) and 21% of chemotherapy‐naïve subjects (n = 34). CTC declines ≥50% were seen in 78% of all treated (n = 77; number of subjects with ≥5 CTCs at baseline and a posttreatment result) and 89% of chemotherapy‐naïve subjects (n = 19); 47% of all treated and 53% of chemotherapy‐naïve subjects had a transition from ≥5 to less than 5 CTCs/7.5 mL blood at some point during the study. PSA and CTC reductions were associated with high PSMA expression (CTCs or tumor tissue) and low neuroendocrine serum markers. In the chemotherapy‐experienced group, the best overall radiologic response to PSMA ADC treatment was stable disease in 51 (60.7%) subjects; 5.7% of subjects in the chemotherapy‐naïve group had partial responses. The most common treatment‐related AEs ≥Common Terminology Criteria for AE (CTCAE) grade 3 were neutropenia, fatigue, electrolyte imbalance, anemia, and neuropathy. The most common serious AEs were dehydration, hyponatremia, febrile neutropenia, and constipation. Two subjects who received 2.5 mg/kg died of sepsis.ConclusionsPSMA ADC demonstrated some activity with respect to PSA declines, CTC conversions/reductions, and radiologic assessments in abi/enz treated mCRPC subjects. Clinically significant treatment‐related AEs included neutropenia and neuropathy.