The development of novel molecularly targeted cancer therapeutics remains slow and
expensive with many late-stage failures. There is an urgent need to accelerate this process …

In the past decade, it has been recognized that increasing spending on biomedical research
has not resulted in an increase in the success rate of pharmaceutical and clinical …

Purpose: Preclinical data established IL15 as a homeostatic factor and powerful stimulator of
NK and CD8+ T-cell function, the basis for clinical testing. Experimental Design: A first-in …

Despite more than two decades of publications that offer more innovative model-based
designs, the classical 3+ 3 design remains the most dominant phase I trial design in …

Background Building on earlier work, the toxicity probability interval (TPI) method, we
present a modified TPI (mTPI) design that is calibration-free for phase I trials. Purpose Our …

The primary objective of phase I oncology trials is to find the MTD. The 3+ 3 design is easy to
implement but performs poorly in finding the MTD. A newer design, such as the modified …

Purpose: To determine the dose-limiting toxicities (DLTs) and maximum tolerated dose
(MTD) of the investigational NEDD8-activating enzyme (NAE) inhibitor pevonedistat (TAK …

A number of novel model-based and model-assisted designs have been proposed to find
the MTD in phase I clinical trials, but their differences and relative pros and cons are not …

Purpose: To evaluate the safety and tolerability in phase I first-in-human combination
therapy with pexidartinib, an inhibitor of colony-stimulating factor-1 receptor, and sirolimus …

Adaptive designs for clinical trials permit alterations to a study in response to accumulating
data in order to make trials more flexible, ethical, and efficient. These benefits are achieved …