“…Dulanermin (rhTRAIL) [62,71,72,73,74,75] did not show clear clinical responses, possibly due to its short half-life (<60 min). DR4-specific agonist mapatumumab [63,76,77,78,79,80,81,82,83], DR5-specific agonists drozitumab [64,65,84], conatumumab [66,67,85], lexatumumab [68,86,87,88,89], HGS-TR2J [90,91], tigatuzumab [69,92,93,94,95,96], and LBY135 [70] were all discontinued after phase 1 or 2 trials without impactful benefits despite their safety (Supplementary Table S1). The reasons why compelling pre-clinical findings with these agonist antibodies did not translate into more robust clinical efficacy remain poorly characterized.…”