Nivolumab Alone and With Ipilimumab in Previously Treated Metastatic Urothelial Carcinoma: CheckMate 032 Nivolumab 1 mg/kg Plus Ipilimumab 3 mg/kg Expansion Cohort Results

Padmanee Sharma, Arlene Siefker-Radtke, Filippo de Braud, Umberto Basso, Emiliano Calvo, Petri Bono, Michael A Morse, Paolo A Ascierto, Jose Lopez-Martin, Peter Brossart, Kristoffer Rohrberg, Begoña Mellado, Bruce S Fischer, Stephanie Meadows-Shropshire, Abdel Saci, Margaret K Callahan, Jonathan Rosenberg

Research output: Contribution to journalArticle

Abstract

PURPOSE: CheckMate 032 is an open-label, multicohort study that includes patients with unresectable locally advanced or metastatic urothelial carcinoma (mUC) treated with nivolumab 3 mg/kg monotherapy every 2 weeks (NIVO3), nivolumab 3 mg/kg plus ipilimumab 1 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (NIVO3+IPI1), or nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks for four doses followed by nivolumab monotherapy 3 mg/kg every 2 weeks (NIVO1+IPI3). We report on the expanded NIVO1+IPI3 cohort and extended follow-up for the NIVO3 and NIVO3+IPI1 cohorts.

METHODS: Patients with platinum-pretreated mUC were enrolled in this phase I/II multicenter study to receive NIVO3, NIVO3+IPI1, or NIVO1+IPI3 until disease progression or unacceptable toxicity. Primary end point was investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, including duration of response.

RESULTS: Seventy-eight patients were treated with NIVO3 (minimum follow-up, 37.7 months), 104 with NIVO3+IPI1 (minimum follow-up, 38.8 months), and 92 with NIVO1+IPI3 (minimum follow-up, 7.9 months). Objective response rate was 25.6%, 26.9%, and 38.0% in the NIVO3, NIVO3+IPI1, and NIVO1+IPI3 arms, respectively. Median duration of response was more than 22 months in all arms. Grade 3 or 4 treatment-related adverse events occurred in 21 (26.9%), 32 (30.8%), and 36 (39.1%) patients treated with NIVO3, NIVO3+IPI1, and NIVO1+IPI3, respectively. Grade 5 treatment-related pneumonitis occurred in one patient each in the NIVO3 and NIVO3+IPI1 arms.

CONCLUSION: With longer follow-up, NIVO3 demonstrated sustained antitumor activity alone and in combination with ipilimumab. NIVO1+IPI3 provided the greatest antitumor activity of all regimens, with a manageable safety profile. This result not only supports additional study of NIVO1+IPI3 in mUC, but demonstrates the potential benefit of immunotherapy combinations in this disease.

Original languageEnglish
Pages (from-to)1608-1616
Number of pages9
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume37
Issue number19
DOIs
Publication statusPublished - Jul 1 2019

Fingerprint Dive into the research topics of 'Nivolumab Alone and With Ipilimumab in Previously Treated Metastatic Urothelial Carcinoma: CheckMate 032 Nivolumab 1 mg/kg Plus Ipilimumab 3 mg/kg Expansion Cohort Results'. Together they form a unique fingerprint.

  • Cite this

    Sharma, P., Siefker-Radtke, A., de Braud, F., Basso, U., Calvo, E., Bono, P., Morse, M. A., Ascierto, P. A., Lopez-Martin, J., Brossart, P., Rohrberg, K., Mellado, B., Fischer, B. S., Meadows-Shropshire, S., Abdel Saci, Callahan, M. K., & Rosenberg, J. (2019). Nivolumab Alone and With Ipilimumab in Previously Treated Metastatic Urothelial Carcinoma: CheckMate 032 Nivolumab 1 mg/kg Plus Ipilimumab 3 mg/kg Expansion Cohort Results. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 37(19), 1608-1616. https://doi.org/10.1200/JCO.19.00538