3687 - Nivolumab (N) Alone or in Combination With Ipilimumab (I) in Patients (pts) With Platinum-Pretreated Metastatic Urothelial Carcinoma (mUC), Including the Nivolumab 1 mg/kg + Ipilimumab 3 mg/kg Expansion From CheckMate 032

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).

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