Meeting
2018 Genitourinary Cancers Symposium
Results of phase I plus expansion cohorts of cabozantinib (Cabo) plus nivolumab (Nivo) and CaboNivo plus ipilimumab (Ipi) in patients (pts) with with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignancies.
Authors
Rosa Maria Nadal
National Institutes of Health, Bethesda, MD
Rosa Maria Nadal , Amir Mortazavi , Mark Stein , Sumanta K. Pal , Nicole N. Davarpanah , Howard L. Parnes , Yang-Min Ning , Lisa M. Cordes , Mohammadhadi H. Bagheri , Liza Lindenberg , Ryan Thompson , Seth M. Steinberg , Tina Moore , Tiffany Lancaster , Milisyaris Velez , Esther Mena , Rene Costello , Donald Bottaro , William L. Dahut , Andrea B. Apolo
Organizations
National Institutes of Health, Bethesda, MD, Arthur G. James Cancer Hospital, Ohio State University Wexner Medical Center, Columbus, OH, Rutgers Cancer Institute of New Jersey, Piscataway, NJ, City of Hope Comprehensive Cancer Center, Duarte, CA, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, National Cancer Institute at the National Institutes of Health, Bethesda, MD, U.S. Food and Drug Administration, Silver Spring, MD, Radiology and Imaging Sciences, Clinical Center, National Institutes of Health, Bethesda, MD, National Institutes of Health, Washington, DC, City of Hope, Duarte, CA, Ohio State University, Columbus, OH, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, Molecular Imaging Program, Center for Cancer Research, National Cancer Institute at the National Institutes of Health, Bethesda, MD, Center for Cancer Research, Division of Cancer Treatment and Diagnosis, Bethesda, MD
Research Funding
NIH
Background: Tolerability and efficacy of CaboNivo and CaboNivoIpi were demonstrated in the initial phase I cohort, prompting longer follow-up and the addition of expansion cohorts to further evaluate both combinations Methods: Phase I cohort had 7 dose levels (DL). Recommended phase 2 doses for CaboNivo=Cabo 40mg/Nivo 3mg/kg (DL2)& CaboNivoIpi=Cabo 40mg/Nivo 3mg/kg/Ipi 1mg/kg (DL6)(Nadal ESMO 2017).In expansion cohorts, pts were treated: [1] DL8: Cabo 40mg/Nivo 1mg/kg/Ipi 3mg/kg; [2]DL2: mUC, metastatic renal cell carcinoma (mRCC), adenocarcinoma bladder (AcB): post-PD-1-PDL1 inhibitor mUC (p-mUC), and [3] DL6 mRCC. Objectives: safety, objective response rate (ORR), duration of response (DOR), progression-free survival (PFS) & overall survival (OS). Results: 75 pts enrolled. Median age 59 yo. 83% male, 17% female. 47 treated with CaboNivo (mUC n=24; AcB n= 9; germ cell tumor (GCT) n= 5; castrate-resistant prostate cancer (CRPC) n= 4; bladder squamous cell carcinoma (SCC) n= 2; penile n=1; mRCC n= 7). 28 treated with CaboNivoIpi: (mUC n=8; penile n=3; CRPC n=7; Sertoli n=1; mRCC n=6; bladder small cell carcinoma n=1; renal medullary carcinoma (RMC) n=2). Any grade (G) adverse events (AEs) (CaboNivo 96% & CaboNivoIpi 96%)/G3–4 AEs (CaboNivo 62% & CaboNivoIpi 71%). Most common any G, CaboNivo: fatigue 70%, diarrhea 60%, AST/ALT 60%, hypophosphatemia (hypoP) 45% & CaboNivoIpi: fatigue 71%, diarrhea 68%, hypoP 50%, AST/ALT 43%. Most common G3-4, CaboNivo: lipase 17%, hypoP 15%, fatigue 6% & CaboNivoIpi: hypoP 21%, AST/ALT 14%, lipase 14%. Selected irAs: colitis (2.6%), hepatitis (2.6%), pneumonitis (2.6%), aseptic meningitis (1.3%). ORR: 36%; 3CR (2mUC, 1SCC) & 20PR (5mUC, 2SCC, 7mRCC, 2Penile, 2AcB, 1CRPC, 1RMC). mDOR: 24.1 mo [95% CI: 14.7-NR], mPFS: 7.2 mo [95%CI: 5.1-18.4], mOS:18.8 mo [95%CI: 10.6-NR]. OS 6/12 mo: 83%/61%. Cohort of p-mUC pts(n=5):1PR/3SD/1PD Conclusions: Updated results from phase I and expanded cohorts confirm initial safety findings and promising antitumor activity for both combinations in mUC, mRCC, and rare GU malignancies Clinical trial information: NCT02496208
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Abstract Details
Session Type
Poster Session
Session Title
Poster Session B: Prostate Cancer, Urothelial Carcinoma, and Penile, Urethral, and Testicular Cancers
Track
Urothelial Carcinoma,Prostate Cancer,Penile, Urethral, and Testicular Cancers
Sub Track
Urothelial Carcinoma
Clinical Trial Registration Number
NCT02496208
Citation
J Clin Oncol 36, 2018 (suppl 6S; abstr 515)
DOI
10.1200/JCO.2018.36.6_suppl.515
Abstract #
515
Poster Bd #
K22
Abstract Disclosures
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