Abstract: SU-OR31
Two-Year Results from a Randomized, Controlled Study of Obinutuzumab for Proliferative Lupus Nephritis
Session Information
- Halfway Through the Marathon: Clinical Candidates in Development
October 25, 2020 | Location: Simulive
Abstract Time: 05:00 PM - 07:00 PM
Category: Glomerular Diseases
- 1203 Glomerular Diseases: Clinical, Outcomes, and Trials
Authors
- Rovin, Brad H., Ohio State University, Columbus, Ohio, United States
- Aroca Martinez, Gustavo, Simon Bolivar University y Clinica de la Costa, Barranquilla, Colombia
- Alvarez, Analia, CEMIC, Buenos Aires, Argentina
- Fragoso loyo, Hilda Esther, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico
- Zuta, Adolfina Elizabeth, Instituto de Ginecología y Reproducción, Lima, Peru
- Furie, Richard, Northwell Health, Great Neck, New York, United States
- Brunetta, Paul Gardner, Genentech, Inc, South San Francisco, California, United States
- Schindler, Thomas, F. Hoffmann-La Roche AG, Basel, Switzerland
- Hassan, Imran, Hoffmann-La Roche Ltd, Mississauga, Ontario, Canada
- Cascino, Matthew, Genentech, Inc, South San Francisco, California, United States
- Garg, Jay P., Genentech, Inc, South San Francisco, California, United States
- Malvar, Ana, Organizacion Maedica de Investigacion, Buenos Aires, Argentina
Background
NOBILITY demonstrated improved renal responses and complete B-cell depletion with the humanized type II anti-CD20 monoclonal antibody obinutuzumab (OBI) compared with placebo (PBO) through 18 months in patients with proliferative lupus nephritis (LN) when added to standard of care therapies. Two-year results from NOBILITY are reported here.
Methods
Patients with class III/IV LN received mycophenolate and steroids and were randomized to OBI or PBO. The primary endpoint was complete renal response (CRR) at week 52. Patients were followed through week 104. Secondary endpoints included overall renal response (ORR) and modified CRR (mCRR).
Results
CRR was greater with OBI than PBO at week 52 (35% vs. 23%, P = 0.115), week 76 (40% vs. 18%, P = 0.007), and week 104 (41% vs 23%, P = 0.026; Table). At week 104, OBI patients had greater improvement in eGFR (+6.5 vs. -3.2 mL/min/1.73 m2, P = 0.018), UPCR, anti-dsDNA, C3, and C4. Serious adverse events (OBI 25% vs. PBO 30%), serious infections (8% vs. 18%) and deaths (1 vs. 4) were not increased with OBI.
Conclusion
NOBILITY demonstrated a sustained benefit of OBI through week 104, approximately 18 months after the final OBI infusion. There were no unexpected safety findings. OBI use in LN will be further evaluated in the Phase 3 REGENCY trial.
Table. Week 104 Results
| Week 104 Endpoint | OBI (n=63) | PBO (n=62) | Difference (80% CI) | P Value |
| CRR | 41% | 23% | 19% (8, 29) | 0.026 |
| ORR | 54% | 29% | 25% (14, 36) | 0.005 |
| mCRR | 56% | 33% | 22% (11, 33) | 0.015 |
| C3 >90 mg/dL | 76% | 47% | 29% (19, 40) | 0.008 |
| C4 >10 mg/dL | 95% | 74% | 21% (13, 29) | 0.001 |
| Mean change in eGFR from baseline (mL/min/1.73 m2) | +6.5 | -3.2 | 9.7 (1.7, 18) | 0.018 |
| Mean change in UPCR from baseline | -2.3 | -1.4 | -0.96 (-1.4, -0.57) | 0.002 |
CRR=UPCR <0.5, serum creatinine (SCr) ≤upper limit of normal (ULN) and ≤115% of baseline, <10 red blood cells per high power field (RBCs/HPF), and no RBC casts. ORR = CRR or partial renal response=UPCR <1 (<3 if baseline UPCR ≥3) and ≤50% of baseline, SCr ≤115% of baseline, and ≤50% increase in urinary RBCs (or <10 RBCs/HPF). mCRR = UPCR <0.5, SCr ≤ ULN.