Nivolumab (N) Alone or in Combination With Ipilimumab (I) in Patients (pts) With Platinum-Pretreated Metastatic Urothelial Carcinoma (mUC), Includi...

Date 20 October 2018
Event ESMO 2018 Congress
Session Proffered paper session - Genitourinary tumours, non prostate
Topics Urothelial Cancers
Presenter Jonathan Rosenberg
Authors J.E. Rosenberg1, P. Sharma2, F.G.M. de Braud3, U. Basso4, E. Calvo5, P. Bono6, M. Morse7, P.A. Ascierto8, J.A. Lopez-Martin9, P. Brossart10, K.S. Rohrberg11, N. Reguart12, W.H. Lin13, S. Meadows-Shropshire14, A. Saci15, M. Callahan1, A.O. Siefker-Radtke16
  • 1Medicine, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 2Genitourinary Medical Oncology, MD Anderson Cancer Center, 77030-4095 - Houston/US
  • 3Medical Oncology & Haematology, Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 4Medical Oncology, Istituto Oncologico Veneto IOV IRCCS, 35128 - Padua/IT
  • 5Start Madrid- Ciocc, Centro Integral Oncológico Clara Campal, 28050 - Madrid/ES
  • 6Comprehensive Cancer Center, Helsinki University Hospital, 00029 - Helsinki/FI
  • 7Medical Oncology, Duke University Medical Center, 27710 - Durham/US
  • 8Melanoma, Cancer Immunotherapy And Development Therapeutics Unit, Istituto Nazionale Tumori Fondazione G. Pascale, 80131 - Naples/IT
  • 9Medical Oncology, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 10Hematology-oncology, University Hospital of Bonn, 53105 - Bonn/DE
  • 11Oncology, Rigshospitalet, University Hospital of Copenhagen, 2100 - Copenhagen/DK
  • 12Oncology, Hospital Clinic of Barcelona, 08036 - Barcelona/ES
  • 13Bms Clinical, Bristol Myers Squibb, 08536 - Princeton/US
  • 14Global Biometric Sciences, Bristol-Myers Squibb, 08536 - Princeton/US
  • 15Clinical Biomarkers, Bristol-Myers Squibb, 08648 - Princeton/US
  • 16Genitourinary Medical Oncology, MD Anderson Cancer Center, 77030-3721 - Houston/US



CheckMate 032 is a multi-cohort study which included N monotherapy (3 mg/kg; N3) and 2 different regimens of N+I (N 3mg/kg + I 1mg/kg [N3I1] or N 1 mg/kg + I 3 mg/kg [N1I3]) treatment in pts with platinum-pretreated mUC. We previously reported an objective response rate (ORR) of 26% with both N3 (n=78) and N3I1 (n=104), and a preliminary ORR of 38% with N1I3 (n=26). Here we report on the expanded N1I3 cohort and extended follow-up data.


This multicenter, open-label study enrolled pts with previously treated locally advanced or mUC, RECIST v1.1 measurable disease, and ECOG performance status ≤1. Pts received either N3 Q2W, N3I1 Q3W for 4 cycles followed by N3 Q2W, or N1I3 Q3W for 4 cycles followed by N3 Q2W until disease progression or unacceptable toxicity. Pts in the N3 cohort could cross over to N3I1 upon progression. The primary endpoint was investigator-assessed ORR per RECIST v1.1 with duration of response (DOR). Secondary endpoints included investigator-assessed progression-free survival (PFS), overall survival (OS), and safety.


With a minimum follow-up of 37.7 mo (N3; n=78), 38.8 mo (N3I1; n=104), and 7.9 mo (N1I3; n=92), ORR was 26%, 27%, and 38%, respectively (Table). Most pts were heavily pretreated. The ORR with N1I3 was highest in pts with PD-L1 ≥1% (58%; Table). Median PFS and OS were numerically longer with N1I3 (Table). Grade 3 or 4 treatment-related adverse events (TRAEs) occurred in 21 (27%), 32 (31%), and 36 (39%) pts with N3, N3I1, and N1I3, respectively. One pt each in the N3 and N3I1 arms had a grade 5 TRAE (pneumonitis).







Minimum follow-up, mo




ORR (95% CI), %

26 (16–37)

27 (19–37)

38 (28–49)

PD-L1 ≥1%

27 (12–48)

35 (19–55)

58 (39–76)

PD-L1 <1%

26 (14–41)

25 (14–38)

24 (12–40)

Median DOR (95% CI), mo

30.5 (8.3–NE)

22.3 (12.8–NE)

22.9 (9.8–NE)

Median PFS (95% CI), mo

2.8 (1.5–5.3)

2.6 (1.4–3.9)

4.9 (2.7–6.6)

Median OS (95% CI), mo

9.9 (7.3–21.1)

7.4 (5.6–11.0)

15.3 (10.1–27.6)

NE, not estimable


The combination of N1I3 demonstrated higher ORR and longer PFS and OS than previous reports of PD-1/PD-L1 monotherapies in this PD-L1 unselected pt population with a manageable safety profile. These results support the ongoing phase 3 trial of N1I3 vs chemotherapy in previously untreated mUC (CheckMate 901; NCT03036098).

Clinical trial identification


Editorial Acknowledgement

Professional medical writing and editorial assistance was provided by Nicolette Belletier and Lawrence Hargett of PPSI (a PAREXEL company), funded by Bristol-Myers Squibb