PC14586 is a first-in-class, oral, small molecule p53 reactivator that is selective for the TP53 Y220C mutation.~The primary objective of Phase 1 monotherapy is to establish the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D) of PC14586. Secondary objectives are to characterize the pharmacokinetic (PK) properties, safety and tolerability, and to assess preliminary efficacy including overall response rate (ORR).~The primary objective of Phase 1b Combination Therapy Treatment Arm is to establish the MTD/RP2D of PC14586 when administered in combination with pembrolizumab. Secondary objectives of Phase 1b Combination Therapy Treatment Arm are to characterize PK, safety and tolerability, and to assess preliminary efficacy of PC14586 when administered in combination with pembrolizumab, including ORR.~The primary objective of Phase 2 monotherapy is to assess the ORR as determined by blinded independent central review. Secondary objectives of include the safety, PK properties, quality of life, and other efficacy measures of PC14586 at the RP2D.
This study will assess the safety, tolerability, and efficacy of multiple dose levels of PC14586 alone and in combination with pembrolizumab in participants with advanced solid tumors containing a TP53 Y220C mutation.