8-K: Syros Pharmaceuticals Presents Phase 2 AML Trial Data at Hematology Conference

Syros Pharmaceuticals presented interim results from its Phase 2 SELECT-AML-1 trial, indicating that adding tamibarotene to venetoclax and azacitidine did not improve response rates in AML patients with RARA overexpression.

Summary

• Syros Pharmaceuticals presented a poster at the Society of Hematologic Oncology 12th Annual Meeting on September 4, 2024, detailing interim results from the SELECT-AML-1 Phase 2 trial.
• The trial investigated the combination of tamibarotene, venetoclax, and azacitidine (tami/ven/aza) versus venetoclax and azacitidine (ven/aza) in adult patients with previously untreated acute myeloid leukemia (AML) who have RARA overexpression and are ineligible for standard induction therapy.
• The study enrolled 51 participants, with 25 receiving tami/ven/aza and 26 receiving ven/aza.
• An interim analysis of the first 40 participants showed similar overall response rates and complete remission/complete remission with incomplete hematologic recovery (CR/CRi) rates between the two treatment arms.
• The CR/CRi rate was 69% in the tami/ven/aza arm and 60% in the ven/aza arm.
• A futility analysis suggested a low likelihood of demonstrating superiority of the triplet regimen over the doublet at the final analysis of 80 participants.
• The study also included a salvage arm where 2 participants who relapsed on ven/aza achieved a response with the addition of tamibarotene.
• The median duration of exposure was 2.2 months for tami/ven/aza and 2.4 months for ven/aza.
• The study is now closed to further enrollment but will continue to evaluate the longer-term impact of tamibarotene.

Sentiment

Score: 4

Explanation: The sentiment is moderately negative due to the lack of improved response rates with the triplet regimen and the futility analysis, despite the well-tolerated safety profile and some positive salvage results.

Positives

• The combination of tamibarotene with venetoclax and azacitidine was well tolerated with no new safety signals.
• The salvage arm showed encouraging preliminary clinical activity, with two participants responding to the addition of tamibarotene after relapsing on venetoclax and azacitidine.
• The study provides an opportunity to evaluate the longer-term impact of tamibarotene on duration of response and survival.

Negatives

• The addition of tamibarotene to venetoclax and azacitidine did not increase response rates compared to venetoclax and azacitidine alone.
• A futility analysis suggests a low likelihood of demonstrating superiority of the triplet regimen at the final analysis.
• The study is now closed to further enrollment, limiting the potential for additional data.

Risks

• The lack of increased response rates with the triplet regimen may impact the future development of tamibarotene in this specific patient population.
• The futility analysis raises concerns about the potential for the study to meet its primary endpoint.
• The study is closed to further enrollment, which may limit the ability to gather additional data or explore alternative treatment strategies.

Future Outlook

The study is closed to further enrollment, but the longer-term impact of tamibarotene on duration of response, survival, and salvage therapy will be evaluated in participants continuing in follow-up.

Industry Context

The study addresses the need for improved treatments for AML patients with RARA overexpression, a subset of patients with a poor prognosis. The results suggest that the addition of tamibarotene to venetoclax and azacitidine may not provide a significant benefit in this population, which could influence future research and treatment strategies in this area.

Comparison to Industry Standards

• The study compares the combination of tamibarotene, venetoclax, and azacitidine to the standard of care venetoclax and azacitidine in AML patients ineligible for intensive chemotherapy.
• The study references a prior Phase 2 study with a 61% CR/CRi rate using tamibarotene and azacitidine, which is similar to the results observed in the current study, suggesting no added benefit from venetoclax.
• The document cites a study showing that approximately one-third of patients do not achieve CR/CRi with venetoclax/azacitidine alone, and nearly all relapse, highlighting the need for new treatment options.
• The study also references a median overall survival of 2.4 months for relapsed patients, emphasizing the poor prognosis and the need for improved therapies.

Stakeholder Impact

• The results may disappoint investors who were hoping for a more significant improvement in response rates with the triplet regimen.
• The lack of increased efficacy may impact the future development of tamibarotene in this specific patient population.
• The study provides valuable data for clinicians treating AML patients with RARA overexpression.

Next Steps

• Evaluate the longer-term impact of tamibarotene on duration of response, survival, and salvage therapy in participants continuing in follow-up.

Key Dates

Keywords

AML, tamibarotene, venetoclax, azacitidine, RARA overexpression, hematology, clinical trial, cancer, leukemia, SELECT-AML-1