Dr. Rampal on the Potential Utilization of Navtemadlin in Relapsed/Refractory AML and MPNs

Raajit K. Rampal, MD, PhD, hematologic oncologist, Memorial Sloan Kettering Cancer Center, discusses the potential utilization of navtemadlin (KRT-232) in relapsed/refractory acute myeloid leukemia (AML) and patients with blast phase myeloproliferative neoplasm (MPN) in a phase 1b/2 trial (NCT04113616). 

This actively accruing trial is examining the safety and efficacy of navtemadlin, a novel oral small molecule MDM2 inhibitor in patients with AML and MPNs.

Few agents have proven efficacious in the treatment of MPNs, leaving the treatment landscape somewhat barren, Rampal says. Conventional anti-AML chemotherapy has not demonstrated much efficacy outside a small subset of patients who will receive an allogeneic stem cell transplant, Rampal explains.

Treatments based around hypomethylating agents (HMAs) also have limitations, and most patients will not have a true remission, Rampal continues. Venetoclax has been added to HMAs to treat patients with MPNs, and the response rates seen across studies falls in the 40% range with associated toxicities, Rampal adds.

The goal is to evaluate if navtemadlin can generate a more profound effect and provide a signal as a single agent, Rampal says. Studies of combinations featuring navtemadlin could come in the future, Rampal adds.

MDM2, which binds to and inhibits the action of P53, is upregulated in patients with MPNs, Rampal concludes.