Cabozantinib plus Nivolumab Phase I Expansion Study in Patients with Metastatic Urothelial Carcinoma Refractory to Immune Checkpoint Inhibitor Therapy

Daniel M. Girardi, Scot A. Niglio, Amir Mortazavi, Rosa Nadal, Primo Lara, Sumanta K. Pal, Biren Saraiya, Lisa Cordes, Lisa Ley, Olena Sierra Ortiz, Jacqueline Cadena, Carlos Diaz, Hadi Bagheri, Bernadette Redd, Seth M. Steinberg, Rene Costello, Keith S. Chan, Min Jung Lee, Sunmin Lee, Yunkai YuSandeep Gurram, Heather J. Chalfin, Vladimir Valera, William D. Figg, Maria Merino, Antoun Toubaji, Howard Streicher, John J. Wright, Elad Sharon, Howard L. Parnes, Yang Min Ning, Donald P. Bottaro, Liang Cao, Jane B. Trepel, Andrea B. Apolo*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Purpose: This study investigated the efficacy and tolerability of cabozantinib plus nivolumab (CaboNivo) in patients with metastatic urothelial carcinoma (mUC) that progressed on checkpoint inhibition (CPI). Patients and Methods: A phase I expansion cohort of patients with mUC who received prior CPI was treated with cabozantinib 40 mg/day and nivolumab 3 mg/kg every 2 weeks until disease progression/unacceptable toxicity. The primary goal was objective response rate (ORR) per RECIST v.1.1. Secondary objectives included progression-free survival (PFS), duration of response (DoR), overall survival (OS), safety, and tolerability. Results: Twenty-nine out of 30 patients enrolled were evaluable for efficacy. Median follow-up was 22.2 months. Most patients (86.7%) received prior chemotherapy and all patients received prior CPI (median seven cycles). ORR was 16.0%, with one complete response and three partial responses (PR). Among 4 responders, 2 were primary refractory, 1 had a PR, and 1 had stable disease on prior CPI. Median DoR was 33.5 months [95% confidence interval (CI), 3.7–33.5], median PFS was 3.6 months (95% CI, 2.1–5.5), and median OS was 10.4 months (95% CI, 5.8–19.5). CaboNivo decreased immunosuppressive subsets such as regulatory T cells (Tregs) and increased potential antitumor immune subsets such as nonclassical monocytes and effector T cells. A lower percentage of monocytic myeloid-derived suppressor cells (M-MDSC) and polymorphonuclear MDSCs, lower CTLA-4 and TIM-3 expression on Tregs, and higher effector CD4þ T cells at baseline were associated with better PFS and/or OS. Conclusions: CaboNivo was clinically active, well tolerated, and favorably modulated peripheral blood immune subsets in patients with mUC refractory to CPI.

Original languageEnglish
Pages (from-to)1353-1362
Number of pages10
JournalClinical Cancer Research
Issue number7
StatePublished - 1 Apr 2022
Externally publishedYes


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