First-In-Human Phase 1 Clinical Trials - A Single-Center Experience In The Era Of Modern Oncotherapeutics.

ABSTRACT

In the era of precision medicine the treatment options for cancer patients and subsequent outcomes are expected to improve. We present a review of patients enrolled in first-in-human Phase1 trials at University of Alabama at Birmingham. Between 1/2015-6/2017, 162 cancer patients (whole cohort, WC) were enrolled on phase1 studies receiving either targeted therapy (TT) or immuno-therapy (IOT). We assessed 90 day mortality (90DM) and time to treatment failure (TTF) to determine the predictors. Of the WC (122 (TT), 40 (IOT)), 90 (56%) received ≥ 2 prior therapies and 38 (24%) ⩾ 5 prior therapies. Overall, Grade 3 or 4 events were observed in 33% (WC) vs 31% (TT) vs 38% (IOT). The 90DM was 9.3% (WC) vs 7.4% (TT) vs 15% (IOT). The median TTF was 4.2 months vs 4.5 m vs 3.6 m. The number of lines of prior therapy and performance status were identified as outcome predictors. Our data reflects the new trend in precision oncology where majority received non-cytotoxic therapeutic interventions. The observation that number of lines of prior therapy and performance status predictive of PFS and 90DM emphasizes the need to consider phase1 trials earlier, preferably upon progression following definitive therapy.