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
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 Disclosures
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