New Combo Therapy May Be a Better Option for Patients with Specific Mutation

By Kim Polacek, APR, CPRC - January 21, 2021

Genetic variances or mutations can increase your risk of developing cancer. One of the more common mutations occurs in the tumor suppressor gene TP53. More than half of all cancers arise from this mutation, and studies have shown that this mutation can lead to more aggressive disease and poorer outcomes.

TP53 mutations are found in roughly 10% to 20% of patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) and up to 40% of patients with therapy related disease. Standard of care for these patients include treatment with azacitidine, a type of chemotherapy known as a hypomethylating agent. Hypomethylating agents affect the way certain genes inside the cells are controlled and can activate death in cells that are rapidly dividing. While this type of therapy can lead to remission for a small percentage of patients, survival is poor ranging from five to nine months.

Dr. David Sallman
Dr. David Sallman, Malignant Hematology Department

“Patients with TP53-mutant disease don’t have many options for therapy with nondurable responses to standard therapy,” said Dr. David Sallman, assistant member of the Malignant Hematology Department at Moffitt Cancer Center. “There is clearly a need for new targeted therapies for this patient population.”

Sallman is leading a national, multicenter clinical trial investigating a new therapy option for this group of patients. It builds upon the standard of care therapy, combining eprenetapopt (APR-246) with azacitidine. Eprenetapopt is a small molecule administered via infusion. Once in the body, it induces cell death in TP53 mutant cancer cells. It also has a synergistic effect when combined with azacitidine, meaning not only do the drugs work well on their own, but together they provide an amplified response.

Fifty-five patients, including AML and MDS patients with at least one TP53 mutation, participated in the phase 1b/2 trial. Sallman says the results are promising.

“We found that 71% of patients responded to the therapy with 44% having a complete response (50% in MDS patients), meaning no sign of disease and return of normal hematopoiesis,” he said. “The combination therapy also leads to a favorable overall survival versus historical outcomes in this patient population, including patients bridged to allogeneic stem cell transplantation.”

The study is now in phase 3, and if results continue to show patient benefit, the combo therapy could be considered for U.S. Food and Drug Administration approval.

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Kim Polacek, APR, CPRC Senior PR Account Coordinator 813-456-3342 More Articles


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