Impact of immune checkpoint inhibitor dose on toxicity, response rate, and survival: A pooled analysis of dose escalation phase 1 trials.

3077Background: PK and PD studies demonstrate drug exposure and target saturation of immune checkpoint inhibitors (ICI) at doses below MTD. MTD remains a primary endpoint in ICI phase 1 trials and the optimal dosing to minimize toxicity and optimize response remains unclear. Methods: We analyzed clinical data from pts treated in phase 1 ICI dose escalation trials at MD Anderson Center for Targeted Therapy. Patients were stratified into a low-dose [LDG] ( 100% MTD) group. Groups were compared for irAE, PFS, OS, ORR (CR + PR), and DCR (CR + PR + SD > 6 months). Results: Among 90 pts treated with escalating doses of ICI (57 CTLA4- and 33 PD1-based) between April 2013 and December 2015, median age was 59 years (range: 20-86 years) and 37 (41%) were females. The most common tumor types treated included renal cell carcinoma (n = 23; 25%), melanoma (n = 16; 18%), sarcoma (n = 10; 11%), and GIST (n = 10; 11%). ...