Dr Ball on Prior Research Supporting the SELECT-AML-1 Trial in Newly Diagnosed AML

Brian C. Ball, assistant professor, Division of Leukemia, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, discusses previous research on tamibarotene in newly diagnosed acute myeloid leukemia (AML), and how these data support the ongoing phase 2 SELECT-AML-1 trial (NCT04905407).

The oral selective retinoic acid receptor alpha (RARA) tamibarotene was previously evaluated in combination with azacitidine (Vidaza) for patients with RARA-positive AML in the phase 2 SY-1425-201 trial (NCT02807558). In this trial, this doublet was shown to be well tolerated, and its toxicity profile was comparable with that of azacitidine monotherapy, Ball reports. Although this study was primarily focused on safety, the preliminary efficacy analysis showed that tamibarotene plus azacitidine produced an overall response rate (ORR) of 67% in patients with RARA-positive AML compared with 39% in patients with RARA-negative AML, Ball adds.

The open-label, SELECT-AML-1 trial was designed to evaluate the effect of adding tamibarotene to this standard-of-care (SOC) backbone in a subgroup of patients with RARA-overexpressing AML who are elderly or unfit for intensive chemotherapy, Ball continues. Patients with monocytic AML often develop venetoclax resistance, and do not typically experience significant benefit with this SOC doublet, Ball states. However, tamibarotene is hypothesized to improve the regimen's tolerability while still enhancing the efficacy of azacitidine and venetoclax for these patients. Due to tamibarotene's ability to induce differentiation, the agent may specifically mitigate the incidence of cytopenias and reduce myelosuppression, Ball explains. The former toxicity is commonly associated with azacitidine and venetoclax use in this disease setting, Ball says.

Initial data from the safety lead-in of this trial showed that the triplet combination did not increase toxicity relative to the azacitadine and venetoclax doublet. Moreover, the agent also demonstrated clinical activity, with a complete response rate of 83%.

Based on these data, the next portion of the SELECT-AML-1 trial will begin. This trial will investigate the regimen’s efficacy and safety in patients with AML whose tumors have RARA overexpression, and is currently ongoing.