TY - JOUR
T1 - Final Results From a Phase I Trial and Expansion Cohorts of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced/Metastatic Genitourinary Tumors
AU - Apolo, Andrea B.
AU - Girardi, Daniel M.
AU - Niglio, Scot A.
AU - Nadal, Rosa
AU - Kydd, Andre R.
AU - Simon, Nicholas
AU - Ley, Lisa
AU - Cordes, Lisa M.
AU - Chandran, Elias
AU - Steinberg, Seth M.
AU - Lee, Sunmin
AU - Lee, Min Jung
AU - Rastogi, Shraddha
AU - Sato, Nahoko
AU - Cao, Liang
AU - Banday, A. Rouf
AU - Boudjadi, Salah
AU - Merino, Maria J.
AU - Toubaji, Antoun
AU - Akbulut, Dilara
AU - Redd, Bernadette
AU - Bagheri, Hadi
AU - Costello, Rene
AU - Gurram, Sandeep
AU - Agarwal, Piyush K.
AU - Chalfin, Heather J.
AU - Valera, Vladimir
AU - Streicher, Howard
AU - Wright, John Joseph
AU - Sharon, Elad
AU - Figg, William D.
AU - Parnes, Howard L.
AU - Gulley, James L.
AU - Saraiya, Biren
AU - Pal, Sumanta K.
AU - Quinn, David
AU - Stein, Mark N.
AU - Lara, Primo N.
AU - Bottaro, Donald P.
AU - Mortazavi, Amir
N1 - Publisher Copyright:
© 2024 by American Society of Clinical Oncology.
PY - 2024/9/1
Y1 - 2024/9/1
N2 - PURPOSE 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. METHODS 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). RESULTS 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. CONCLUSION 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.
AB - PURPOSE 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. METHODS 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). RESULTS 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. CONCLUSION 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.
UR - http://www.scopus.com/inward/record.url?scp=85202819879&partnerID=8YFLogxK
U2 - 10.1200/JCO.23.02233
DO - 10.1200/JCO.23.02233
M3 - Article
C2 - 38954785
AN - SCOPUS:85202819879
SN - 0732-183X
VL - 42
SP - 3033
EP - 3046
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 25
ER -