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Genitourinary tumours, non-prostate

4232 - A phase I study of cabozantinib plus nivolumab (CaboNivo) in patients (pts) refractory metastatic urothelial carcinoma (mUC) and other genitourinary (GU) tumors


09 Oct 2016


Genitourinary tumours, non-prostate


Andrea Apolo


Annals of Oncology (2016) 27 (6): 266-295. 10.1093/annonc/mdw373


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

Author affiliations

  • 1 Genitourinary Malignancies Branch, Center for Cancer Research-National Cancer Institute, 20892 - Bethesda/US
  • 2 Internal Medicine, Ohio State Univ Medical Center, Columbus/US
  • 3 Division Of Medical Oncology, The Cancer Institute of New Jersey, New Brunswick/US
  • 4 Medical Oncology, City of Hope, 91010 - Duarte/US
  • 5 Medical Oncology, National Cancer Institute, 20892 - Bethesda/US
  • 6 Medical Oncology, The Cancer Institute of New Jersey, 08903 - New Brunswick/US


Abstract 4232


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.

Clinical trial identification


Legal entity responsible for the study





All authors have declared no conflicts of interest.

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