774PD - A phase I study of cabozantinib plus nivolumab (CaboNivo) in patients (pts) refractory metastatic urothelial carcinoma (mUC) and other genitourinar...

Date 09 October 2016
Event ESMO 2016 Congress
Session Genitourinary tumours, non-prostate
Topics Urothelial Cancers
Presenter Andrea Apolo
Citation Annals of Oncology (2016) 27 (6): 266-295. 10.1093/annonc/mdw373
Authors A.B. Apolo1, A. Mortazavi2, M. Stein3, S.K. Pal4, N. Davarpanah1, H.L. Parnes5, Y.M. Ning5, D.C. Francis1, L.M. Cordes1, M. Berniger1, S.M. Steinberg5, P. Monk2, T. Lancaster2, T. Mayer6, R. Costello1, D.P. Bottaro1, W.L. Dahut1
  • 1Genitourinary Malignancies Branch, Center for Cancer Research-National Cancer Institute, 20892 - Bethesda/US
  • 2Internal Medicine, Ohio State Univ Medical Center, Columbus/US
  • 3Division Of Medical Oncology, The Cancer Institute of New Jersey, New Brunswick/US
  • 4Medical Oncology, City of Hope, 91010 - Duarte/US
  • 5Medical Oncology, National Cancer Institute, 20892 - Bethesda/US
  • 6Medical Oncology, The Cancer Institute of New Jersey, 08903 - New Brunswick/US



Cabo is a multiple receptor tyrosine kinase inhibitor primarily targeting MET and VEGFR2. Correlative studies support the theory that cabozantinib has immunomodulatory properties. Nivo is a monoclonal IgG4 antibody to PD-1. We report the safety and clinical activity of the combination of CaboNivo in pts with mUC and other GU tumors (NCT02496208).


This phase I trial used a rolling 6 design. 6 pts were treated at 4 dose levels (DL) for part 1 (CaboNivo) of the study. Pts received Cabo PO daily and Nivo IV q2wks: DL1 Cabo 40mg/Nivo 1mg/kg, DL2 Cabo 40mg/Nivo 3mg/kg, DL3 Cabo 60mg/Nivo1mg/kg, DL4 Cabo 60mg/Nivo 3mg/kg. Tumors were assessed for overall response rate (ORR) q8wks (RECIST 1.1). Adverse events (AEs) were graded (G) by NCI-CTCAE v4.0.


From 7/22/15-5/11/16, 24pts (mUC N = 6; bladder urachal N = 4; bladder squamous cell carcinoma (SCC) N = 3; germ cell tumor (GCT) N = 5; castrate-resistant prostate cancer (CRPC) N = 4; renal cell carcinoma (RCC) N = 1, and trophoblastic tumor N = 1) were treated. Median age was 55 (range 35-75), 21 (88%) were male. 9 pts required dose reductions (N = 2 DL1; N = 1 DL2; N = 2 DL3; N = 4 DL4), for PPE G2 N = 3 (DL1/2/4)); fatigue G1/2 N = 2 (DL3), diarrhea G2 N = 1 (DL3), lipase/amylase elevation G3 (DL1), weight loss G1 N = 1 (DL4), and anorexia/dehydration G2 N = 2 (DL4). Common treatment-related G1/2 AEs were transaminitis N = 20, diarrhea N = 11, hoarseness N = 7, dysgeusia N = 5, thrombocytopenia N = 5, hyponatremia N = 5. Grade 3 AEs included neutropenia N = 3 (DL1), fatigue N = 2 DL2, mucositis N = 1 (DL4), vomiting N = 1 (DL3). There were no G4/5 toxicities, no immune-related AEs and no DLTs. 18 pts were evaluable for response. ORR was 33% 6/18 (1 CR (bladder SCC); 5 PRs (mUC, RCC, urachal, urethral SCC, CRPC). All responses were ongoing at cutoff. SD 38% 7/18.


CaboNivo was well tolerated with no DLTs. Cabo 60mg resulted in more dose reductions due to clinically significant AEs. The recommended dose is Cabo40mg/Nivo3mg/kg. Part II of the phase I (triplet with ipilimumab (CaboNivoIpi) is ongoing. Expansion studies in pts with mUC and RCC are planned.

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All authors have declared no conflicts of interest.