Clinical Trials Under Way

Hoffmann-La Roche’s phase 1 trial for the oral nutlin derivative RG7112, reported in 2016, demonstrated clinical activity against relapsed/refractory AML and CLL, a “proof of concept” demonstration that MDM2 inhibition can restore p53 function and clinical response in hematologic malignancies.16

“RG7112 showed sufficient clinical activity to lead to p53 stabilization and transcriptional activation of p53 target genes in extremely poor prognosis (relapsed/refractory) AML patients and in CLL/sCLL patients,” wrote the authors of a recent review.9 “In AML, RG7112 administration showed clinical activity as monotherapy, particularly in relapsed/refractory AML with some patients reaching complete remission and hematopoietic recovery, allowing subsequent transplantation.”

Researchers are also pursuing several clinical studies of the nutlin derivative RG7388 (idasanutlin) as a potential treatment for a range of hematologic cancers and disorders, including thrombocythemia and polycythemia vera.

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Several preclinical, early phase clinical dose-finding, and safety studies of nutlins, including idasanutlin and RG7112, were reported at the 2017 American Society of Hematology (ASH) 59th Annual Meeting & Exposition in Atlanta, Georgia.

References

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