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Pharmacokinetic analysis unexpectedly indicated a half-life of 9-19days, invalidating the CIVI dosing resulting in discontinuation of the study before the RP2D was defined. PENAO was administered by CIVI at dose levels up to 9mg/m /day with only one DLT noted. Pharmacokinetic studies invalidated the rationale for continuous dosing and led to discontinuation of the trial without defining a RP2D. Future clinical development of PENAO will use intermittent dosing schedule, alone and in combination with rapamycin. PENAO was administered by CIVI