Table 1 p53 reactivating drugs in clinical studies in MDS and AML (for complete list of clinical trials refer to the text)
From: p53 biology and reactivation for improved therapy in MDS and AML
p53 reactivating Mechanism drug | Clinical trial | |
Eprenetapopt (APR-246) | Mutant p53 refolding, restoring wild-type p53 transcription activity and cell death program | Phase Ib NCT00900614: Safety Study of APR-246 in Patients With Refractory Hematologic Cancer or Prostate Cancer1 Phase Ib/II NCT03072043: Safety and Efficacy of APR-246 w/Azacitidine for tx of TP53 Mutant Myeloid Neoplasms1 Phase Ib/II NCT03588078: Study of the Safety and Efficacy of APR-246 in Combination With Azacitidine1 Phase II NCT03931291: APR-246 in Combination With Azacitidine for TP53 Mutated AML (Acute Myeloid Leukemia) or MDS (Myelodysplastic Syndromes) Following Allogeneic Stem Cell Transplant1 Phase III NCT03745716: APR-246 & Azacitidine for the Treatment of TP53 Mutant Myelodysplastic Syndromes (MDS)1 Phase I NCT04214860: APR-246 in Combination With Venetoclax and Azacitidine in TP53-Mutant Myeloid Malignancies1 |
Trisenox (ATO) | Mutant p53 refolding (structural mutants), restoring transcription wild-type p53 activity and cell death program | Phase I NCT03855371: Combination of Decitabine and ATO to Treat AML/MDS Expressing a Classified Type of Mutant p53 |
Atorvastatin | Mutant p53 degrader | Phase I NCT03560882: A pilot trial of atorvastatin in p53-mutant and p53 wild-type malignancies |
RG7112(RO5045337) | MDM2 inhibitor | Phase I NCT00623870: A Study of RO5045337 [RG7112] in Patients With Hematologic Neoplasms1# |
Idasanutlin (RG7388) | MDM2 inhibitor | Phase I/Ib NCT01773408: A Study of RO5503781 as a single agent or in combination with cytarabine in participants with acute myelogenous leukemia# Phase III NCT02545283: Study of Idasanutlin With Cytarabine Versus Cytarabine Plus Placebo in Participants With Relapsed or Refractory Acute Myeloid Leukemia (AML) (MIRROS)§ |
Navtemadlin (AMG-232) | MDM2 inhibitor | Phase I NCT02016729: Study Evaluating AMG 232 Alone and in Combination With Trametinib in Acute Myeloid Leukemia1 |
Milademetan (DS-3032b) | MDM2 inhibitor | Phase I NCT02319369: Safety, Tolerability and pharmacokinetics of milademetan alone and with 5-azacitidine (AZA) in acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (MDS)1 Phase I/II NCT03634228: Milademetan Tosylate and Low-dose Cytarabine with or without Venetoclax in treating participants with recurrent or refractory acute myeloid leukemia@ |
Siremadlin (HDM201) | MDM2 inhibitor | Phase I NCT02143635: Study to Determine and Evaluate a Safe and Tolerated Dose of HDM201 in Patients With Selected Advanced Tumors That Are TP53wt |
APG-115 | MDM2 inhibitor | Phase Ib/II NCT04358393: A Study of APG-115 Alone or Combined With Azacitidine in Patients With AML, CMML, or MDS |
Sulanemadlin (ALRN-6924) | MDM2/MDM4 inhibitor | Phase I/Ib NCT02909972: Safety Study of ALRN-6924 in Patients With Acute Myeloid Leukemia or Advanced Myelodysplastic Syndrome |