Summary
Lead investigators from the U.S. and French phase Ib/II clinical trials of APR-246 and azacitidine (AZA) in patients with TP53-mutant myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), presented positive data at the 2019 ASH Annual Meeting. Both trials are evaluating the safety and efficacy of APR-24, in combination with azacitidine for the treatment of TP53-mutant MDS and AML.
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Original Article
Positive Data of APR-246 & Azacitidine in Patients with TP53 MDS & AML
Oncology Times
Lead investigators from the U.S. and French phase Ib/II clinical trials of APR-246 and azacitidine (AZA) in patients with TP53-mutant myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), presented positive data at the 2019 ASH Annual Meeting. Both trials are evaluating the safety and efficacy of APR-24, in combination with azacitidine for the treatment of TP53-mutant MDS and AML.
David Sallman, MD, of the Moffitt Cancer Center and lead investigator on the U.S. trial, presented on 33 evaluable MDS patients as of the data cutoff, with an overall response rate (ORR) of 88 percent, and a 61 percent complete remission (CR) rate, by International Working Group (IWG) criteria. With a median duration of follow-up of 10.8 months, the median duration of response was 8.4 months and the median duration of CR was 7.3 months. Seventeen (52%) evaluable MDS patients discontinued therapy to pursue stem cell transplant. Median overall survival (OS) for all enrolled patients (n=55) was 10.8 months. Median OS in responding patients versus non-responders was 13.7 versus 3.9 months. Adverse events, regardless of causality, were mostly grade 1/2. Grade 3+ adverse events occurring in ≥20 percent of patients were limited to cytopenias and infection, consistent with underlying hematopoietic malignancies, and no exacerbation of the expected AZA-related safety profile has been observed.
Prof. Thomas Cluzeau reported preliminary data for 24 evaluable MDS patients enrolled before June 2019 in the French trial being conducted by the Groupe Francophone des Myélodysplasies, which is led by Prof. Pierre Fenaux, who is also the lead investigator of the French trial. Following the oral presentation, the GFM informed Aprea that the analysis presented and previously reported included three MDS patients who achieved a CR but were enrolled after May 2019 and, therefore, should not have been included among the 24 evaluable patients under the specified enrollment cutoff.
In addition, there were two additional MDS patients enrolled before June 2019 who had responded. The updated data for 24 evaluable MDS patients enrolled before June 2019 are ORR of 71 percent and a CR rate of 54 percent by IWG criteria. Inclusive of the CRs in three MDS patients enrolled after May 2019, the updated data for 27 evaluable MDS patients are ORR of 74 percent and CR rate of 59 percent. With a median duration of follow-up of 6.4 months, the median OS for all enrolled patients (n=53) had not been reached. In addition, all responding patients were alive at data cutoff. Relative to baseline, mutant TP53 variant allele frequency was significantly decreased in responding patients and undetectable in all patients who achieved a CR.