First-line Tamibarotene combined with Venetoclax and azacitidine induces 100% CR rate in SELECT-AML-1 trial

Adding the oral selective RARα agonist Tamibarotene (tamibarotene) to venetoclax and azacitidine n>Produced100% complete response (CR; n=7)/CR with incomplete hematological recovery (CRin=2) ratio (n=9) vs. 70% (n=7/1 0; CR, n=3; CRi, n=4), for patients with evaluable response in newly diagnosed RARA-overexpressing acute myeloid leukemia (AML), meeting the primary endpoint of the phase 2 SELECT-AML-1 trial (NCT 04905407).

In a press release describing initial data from the randomized portion of SELECT-AML-1, "Despite recent advances in the treatment of unfit AML patients, there remains a significant need for options that provide higher response rates and improved overall survival, particularly for the one-third of patients who do not respond to existing standard of care." SELECT-AML-1 is evaluating the safety and anti-tumor activity of the triplet regimen compared with venetoclax and azacitidine alone in approximately 80 newly diagnosed AML patients who are not candidates for standard intensive chemotherapy. Of note, patients in the control group who do not respond to combination therapy will be allowed to receive triple therapy as salvage therapy. In December 2022, results from the safety lead-in part of the trial showed that 83% of evaluable patients (n=5/6) achieved CR/Cri.

As of November 13, 2023, 23 patients have been enrolled in the randomized portion of the trial, of which 19 are evaluable for response. The median patient age was 77 years (range, 66-85 years) in the triplet group and 76 years (range, 69-84 years) in the combination group. The median treatment duration was 66 days (range, 8-188 days) in the triplet arm and 75 days (range, 7-277 days) in the combination arm. Other results from the trial showed that the median CR/CRi response was 21 days (range, 14-28 days) in the triplet arm and 25 days (range, 17-56 days) in the combination arm. At the end of the first treatment cycle, all patients in the triplet arm achieved CR/CRi, compared with 60% of patients in the combination arm.

These data highlight the potential of Tamibarotene as a primary therapy for patients with RARA-overexpressing, newly diagnosed, unsuitable AML, further demonstrating its differentiated product profile and validating our biotargeted approach, with first results from a randomized controlled study demonstrating the addition of Tamibarotene to standard of care, venetoclax and azacitidine.potential impact, and importantly, these results are consistent with prior experience. Regarding safety, Triad was generally well tolerated, reflecting previous clinical data from the safety lead-in portion of the trial. Additionally, there are no new safety signals or evidence of increased myelosuppression with triplet. Most non-hematological adverse reactions (AE) were of low grade and reversible, and the incidence of serious AEs was similar between the two groups.

In multiple clinical trials, Tamibarotene was observed to rapidly exert clinically relevant activity and to be well tolerated and safe, including in combination. SELECT-AML-1 is still open for registration. Updated data from the study, including duration of response, minimal residual disease negativity and survival rates, are expected to be released in 2024.