Phase I expansion study of cabozantinib plus nivolumab (CaboNivo) in metastatic urothelial carcinoma (mUC) patients (pts) with progressive disease following immune checkpoint inhibitor (ICI) therapy.
Authors: Daniel da Motta Girardi, Scot Anthony Niglio, Amir Mortazavi, Primo Lara, Sumanta K. Pal, Biren Saraiya, Lisa M. Cordes, Lisa Ley, Olena Sierra Ortiz, Jacqueline Cadena, Carlos Diaz, Mohammadhadi H. Bagheri, Seth M. Steinberg, Rene Costello, Howard Streicher, John Wright, Howard L. Parnes, Yang-Min Ning, Donald P. Bottaro, Andrea B. Apolo
Journal: Journal of Clinical Oncology (2020)

5037 Background: Previous treatment with ICI is more common in clinical practice since recent FDA-approval of 5 ICIs in second-line and 2 in first-line for mUC. There is lack of data regarding the use of ICI after progression on a prior ICI. Cabozantinib has been shown to have immunomodulatory properties and may have synergistic effect with ICI. Methods: This is a phase I expansion cohort of mUC pts, who received prior ICI, treated with Cabozantinib 40mg daily and Nivolumab 3mg/kg every 2 weeks until disease progression/unacceptable toxicity. The primary objective was to determine the efficacy and tolerability of CaboNivo. Results: Twenty-nine mUC pts were treated. Median follow-up was 14.1 months (mo). The majority of pts were male (75.8%); 27 were White (93.1%), and 2 were Asian (6.9%). Primary tumor was bladder in 21 pts (72.4%) and upper tract in 8 (27.6%). Twenty-two pts (75.9%) had visceral metastasis (mets), 4 (13.8%) had lymph node only mets and 13 (44.8%) had liver mets. The median number of prior lines of treatment for mUC was 2 (range 0-8) with 17 pts (58.6%) receiving 2 prior lines of treatment. The majority of pts (86.2%) received prior chemotherapy for mUC and all pts received prior ICI. The median number of cycles of prior ICI was 7 (range 1-20) and median time between previous ICI and CaboNivo was 2.5 mo (range 1-18). The best response to previous ICI was partial response (PR) in 1 pt (3.4%), stable disease (SD) in 13 (44.9%), progressive disease (PD) in 14 (48.3%) and one (3.4%) was not evaluable (NE). The overall response rate for CaboNivo was 13.8% with 4 pts achieving PR (13.8%), 15 SD (51.7%), 7 PD (24.2%) and 3 NE (10.3%). Responses were seen in the liver, lung, and lymph nodes. Among 4 pts with PR, 2 were primary refractory to previous ICI and 2 had SD. At cutoff date the median duration of response was not reached and 3 PR were still ongoing: 1 had just began and the other 2 were ongoing at 12.3 and 26.4 mo. Among 15 pts with SD, 4 had SD for more than 6 mo and 2 were still ongoing at 8.1 and 25.1 mo. Median progression-free survival was 3.6 mo (95% CI: 2.1 – 5.3 mo) and median overall survival was 10 mo (95% CI: 5.8 – 16.7 mo). Grade 1/ 2 treatment related adverse events (AEs) occurred in 28 pts (97%) and &gt;Grade 3 (G&gt;3) AEs occurred in 14 pts (48%). The most common G&gt;3 AEs were fatigue (14%), hypophosphatemia (14%), lymphocyte count decrease (14%), hypertension (7%) and hyponatremia (7%). Conclusions: CaboNivo is clinically active and safe in heavily pretreated pts with progressive mUC following ICI. Clinical trial information: NCT02496208 .