Cabozantinib and nivolumab (CaboNivo) alone or with ipilimumab (CaboNivoIpi) have shown promising efficacy and safety in patients with metastatic urothelial carcinoma (mUC), metastatic renal cell carcinoma (mRCC), and rare genitourinary (GU) tumors in a dose-escalation phase I study. We report the final data analysis of the safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) of the phase I patients and seven expansion cohorts.
This is an investigator-initiated, multicenter, phase I trial. CaboNivo doublet expansion cohorts included (1) mUC, (2) mRCC, and (3) adenocarcinoma of the bladder/urachal; CaboNivoIpi triplet expansion cohorts included (1) mUC, (2) mRCC, (3) penile cancer, and (4) squamous cell carcinoma of the bladder and other rare GU tumors (ClinicalTrials.gov identifier: NCT02496208).
The study enrolled 120 patients treated with CaboNivo (n = 64) or CaboNivoIpi (n = 56), with a median follow-up of 49.2 months. In 108 evaluable patients (CaboNivo n = 59; CaboNivoIpi n = 49), the ORR was 38% (complete response rate 11%) and the median duration of response was 20 months. The ORR was 42.4% for mUC, 62.5% for mRCC (n = 16), 85.7% for squamous cell carcinoma of the bladder (n = 7), 44.4% for penile cancer (n = 9), and 50.0% for renal medullary carcinoma (n = 2). Grade ≥ 3 treatment-related adverse events occurred in 84% of CaboNivo patients and 80% of CaboNivoIpi patients.
CaboNivo and CaboNivoIpi demonstrated clinical activity and safety in patients with multiple GU malignancies, especially clear cell RCC, urothelial carcinoma, and rare GU tumors such as squamous cell carcinoma of the bladder, small cell carcinoma of the bladder, adenocarcinoma of the bladder, renal medullary carcinoma, and penile cancer.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2024 Jul 02 [Epub ahead of print]
Andrea B Apolo, Daniel M Girardi, Scot A Niglio, Rosa Nadal, Andre R Kydd, Nicholas Simon, Lisa Ley, Lisa M Cordes, Elias Chandran, Seth M Steinberg, Sunmin Lee, Min-Jung Lee, Shraddha Rastogi, Nahoko Sato, Liang Cao, A Rouf Banday, Salah Boudjadi, Maria J Merino, Antoun Toubaji, Dilara Akbulut, Bernadette Redd, Hadi Bagheri, Rene Costello, Sandeep Gurram, Piyush K Agarwal, Heather J Chalfin, Vladimir Valera, Howard Streicher, John Joseph Wright, Elad Sharon, William D Figg, Howard L Parnes, James L Gulley, Biren Saraiya, Sumanta K Pal, David Quinn, Mark N Stein, Primo N Lara, Donald P Bottaro, Amir Mortazavi
Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Biostatistics and Data Management Section, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Developmental Therapeutics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Molecular Targets Core, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD., Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Investigational Drug Branch, Cancer Therapy Evaluation Program, National Cancer Institute, National Institutes of Health, Rockville, MD., Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Bethesda, MD., Center for Onco-Immunology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD., Genitourinary Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ., City of Hope Comprehensive Cancer Center, Duarte, CA., Division of Cancer Medicine and Blood Diseases, Department of Medicine, Genitourinary Oncology, Keck School of Medicine, University of Southern California, Los Angeles, CA., Genitourinary Oncology, Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY., University of California Davis Comprehensive Cancer Center, Sacramento, CA., Division of Medical Oncology, Department of Internal Medicine, College of Medicine, The Ohio State University, and the Comprehensive Cancer Center, Columbus, OH.