RESULTS FROM THE REGENCY TRIAL ASSESSING EFFICACY AND SAFETY OF OBINUTUZUMAB IN ACTIVE LUPUS NEPHRITIS

O025 / #750 Topic: AS15 - Lupus Nephritis-Clinical Late-Breaking Abstract ABSTRACT CONCURRENT SESSION 04: ADVANCING LUPUS THERAPIES AND INSIGHTS 22-05-2025 1:40 PM - 2:40 PM Background/Purpose Obinutuzumab, a humanized type II anti-CD20 monoclonal antibody, is approved for B cell malignancies. In the Phase II NOBILITY trial of patients with active lupus nephritis (LN; NCT02550652 ), study participants receiving obinutuzumab in addition to standard therapy were significantly more likely to achieve complete renal response than those receiving placebo in addition to standard therapy. The results of the Phase III REGENCY trial ( NCT04221477 ), performed to verify NOBILITY, are presented here. Methods REGENCY, a Phase III, double-blind placebo-controlled trial, randomized adults with biopsy-proven active proliferative LN 1:1 to placebo or one of 2 intravenous obinutuzumab dosing schedules (1000 mg: Day 1, Weeks 2, 24, 26, ±50 and 52) in addition to standard therapy. The primary endpoint was complete renal response (CRR, defined as urine protein-to-creatinine ratio [UPCR] <0.5 g/g, estimated glomerular filtration rate [eGFR] ≥85% of baseline and no intercurrent events of rescue therapy, treatment failure, death or early study withdrawal) at Week 76 and assessed in the intention-to-treat population. Key secondary endpoints included CRR at Week 76 with successful prednisone taper to ≤7.5 mg/day between Weeks 64 and 76, and UPCR <0.8 g/g at Week 76 with no intercurrent events, change in eGFR from baseline to Week 76 and renal-related events or death through Week 76. Incidence and severity of adverse events through Week 76 were compiled. Results Of 271 patients randomized, 135 were randomized to obinutuzumab and 136 to placebo. At Week 76, 46.4% of patients in the obinutuzumab group and 33.1% in the placebo group achieved CRR (adjusted difference, 13.4%; 95% CI, 2.0% to 24.8%; P =0.0232). More patients in the obinutuzumab group achieved CRR at Week 76 with successful prednisone taper (42.7% vs 30.9%, adjusted difference, 11.9%; 95% CI, 0.6% to 23.2%; P =0.0421) and a proteinuric response (UPCR <0.8 g/g) with no intercurrent events at Week 76 (55.5% vs 41.9%; adjusted difference, 13.7%; 95% CI, 2.0% to 25.4%; P =0.0227). Numerical changes in eGFR from baseline to Week 76 favored obinutuzumab compared with placebo, and fewer patients in the obinutuzumab group experienced the composite outcome of death or renal-related events through Week 76. Prespecified subgroup analyses demonstrated numerically greater CRR rates with obinutuzumab in patients with potentially more active disease at enrollment, such as those with Class IV LN, concomitant class V disease, baseline UPCR ≥3 g/g or greater baseline serologic activity. No new safety signals were observed based on the established safety profile of obinutuzumab in oncology indications. More coronavirus disease 2019 (COVID-19) events were observed in the obinutuzumab group, which primarily occurred during the acute phase of the COVID-19 pandemic. There were 3 deaths in the obinutuzumab group and 1 in the placebo group, which were mainly complications of COVID-19. Conclusions Obinutuzumab plus standard therapy was more effective than placebo plus standard therapy for achieving CRR, a clinically meaningful surrogate of kidney function, in patients with LN, while exhibiting an acceptable safety profile.

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