Primate Monocytes - CD14, CD16 - Ziegler-Heitbrock


Cabozantinib Plus Nivolumab Phase I Expansion Study in Metastatic Urothelial Carcinoma Patients Refractory to Immune Checkpoint Inhibitor Therapy.


PURPOSE: This study investigated the efficacy and tolerability of cabozantinib plus nivolumab (CaboNivo) in patients with metastatic urothelial carcinoma (mUC) that progressed on checkpoint inhibition (CPI). EXPERIMENTAL DESIGN: A phase I expansion cohort of mUC patients who received prior CPI was treated with cabozantinib 40 mg/day and nivolumab 3 mg/kg every 2 weeks until disease progression/unacceptable toxicity. The primary goal was objective response rate (ORR) per RECIST v.1.1. Secondary objectives included progression-free survival (PFS), duration of response (DoR), overall survival (OS), safety, and tolerability. RESULTS: 29/30 patients enrolled were evaluable for efficacy. Median follow-up was 22.2 months. Most patients (86.7%) received prior chemotherapy and all patients received prior CPI (median 7 cycles). ORR was 16.0%, with one complete response and 3 partial responses (PRs). Among 4 responders, 2 were primary refractory, 1 had a PR, and 1 had stable disease on prior CPI. Median DoR was 33.5 months (95% CI: 3.7-33.5), median PFS was 3.6 months (95% CI: 2.1-5.5), and median OS was 10.4 months (95% CI: 5.8-19.5). CaboNivo decreased immunosuppressive subsets such as regulatory T cells (Tregs) and increased potential antitumor immune subsets such as non-classical monocytes and effector T cells. A lower percentage of monocytic myeloid-derived suppressor cells (M-MDSC) and polymorphonuclear MDSCs (PMN-MDSC), lower CTLA-4 and TIM-3 expression on Tregs, and higher effector CD4+ T cells at baseline were associated with better PFS and/or OS. CONCLUSIONS: CaboNivo was clinically active, well-tolerated, and favorably modulated peripheral blood immune subsets in mUC patients refractory to CPI.

Authors: Girardi DM, Niglio SA, Mortazavi A, Nadal R, Lara P, Pal SK, Saraiya B, Cordes L, Ley L, Sierra Ortiz O, Cadena J, Diaz C, Bagheri H, Redd B, Steinberg SM, Costello R, Chan KS, Lee MJ, Lee S, Yu Y, Gurram S, Chalfin HJ, Valera V, Figg WD, Merino M, Toubaj
Journal: Clin Cancer Res;2022 2022 Apr 1;28(7):1353-1362. doi:10.1158/1078-0432.CCR-21-3726
Year: 2022
PubMed: PMID: 35031545 (Go to PubMed)