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
Immunotherapy
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

Abstract

Background

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.

Methods

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.

Results

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).

N3

n=78

N3I1

n=104

N1I3

n=92

Minimum follow-up, mo

37.7

38.8

7.9

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

Conclusions

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

NCT01928394

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