Evaluation of the clinical activity of ipilimumab (IPI) plus nivolumab (NIVO) in patients (pts) with NIVO-refractory metastatic urothelial cancer (UC).

Genitourinary Cancer
Session Type and Session Title: 
Poster Session B: Prostate Cancer and Urothelial Carcinoma
Abstract Number: 


Poster Board Number: 
Poster Session B Board #H21
J Clin Oncol 35, 2017 (suppl 6S; abstract 384)
Margaret K. Callahan, Brooke Elizabeth Kania, Gopa Iyer, Jessica Mary Clement, Samuel Funt, Asia S. McCoy, Grace Hettich, Etay Ziv, Mark J. Bluth, Phillip Wong, Jedd D. Wolchok, Dean F. Bajorin, Jonathan E. Rosenberg; Memorial Sloan Kettering Cancer Center, New York, NY; University of Connecticut Health Center Carole and Ray Neag Comprehensive Cancer Center, Farmington, CT

Abstract Disclosures


Background: Programmed cell death –1 (PD-1) and its ligand (PD-L1) serve as checkpoints that regulate the interaction between the immune system and tumors. Antibodies blocking PD-1 or PD-L1 enhance antitumor activity in pts with UC. NIVO, a PD-1 blocking antibody, has clinical activity in UC as a single agent. IPI, an antibody blocking the checkpoint molecule CTLA-4, has demonstrated biologic activity in UC. Dual checkpoint blockade with both NIVO and IPI also has clinical activity in UC, but has not been systematically studied in NIVO-refractory UC. We sought to evaluate whether the addition of IPI to NIVO is feasible and clinically beneficial in pts whose UC is refractory to single agent NIVO. Methods: Forty pts with advanced or metastatic UC were treated with NIVO (3 mg/kg every 2 weeks) as part of a single arm, IRB-approved, investigator initiated study (NCT02553642). The study offered the option of treatment with the combination of IPI (1 mg/kg) and NIVO (3 mg/kg) for pts who had confirmed progression after treatment with NIVO monotherapy. The combination was dosed once every 3 weeks for 4 doses and followed by NIVO monotherapy. Pts were monitored for response and toxicity. Results: Ten pts who were refractory to NIVO monotherapy were treated with the combination of IPI and NIVO. There was a modest increase in the frequency of toxicities associated with the combination, compared to NIVO alone. One pt developed grade 3 diarrhea after treatment with the combination. No grade 3/4 toxicities were observed in pts treated with NIVO monotherapy. One pt achieved a confirmed partial response. Three additional pts achieved stable disease after documented progression. Pharmacodynamic changes in peripheral blood immune cells were monitored during treatment with NIVO monotherapy and combination therapy. Conclusions: The combination of IPI and NIVO is well tolerated and may have clinical activity in pts with UC who fail to respond to PD-1 blockade. Further studies to evaluate the magnitude of clinical activity and predictors of response for this combination are needed. Clinical trial information: NCT02553642