616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Novel Targets and Combinations


Conclusion cited from the abstract: The non-chemotherapy combination of Ven+Idasa demonstrated encouraging safety and efficacy in elderly pts with R/R AML who were ineligible for cytotoxic chemotherapy. The anti-leukemic response rate at the dose levels being considered for the RP2D was 50%, with a CR+CRp+CRi rate of 29%. Updated predictive biomarker data will be presented. Evaluation of Ven+Idasa RP2D is ongoing, and will be followed by dose expansion.




Conclusion cited from the abstract: In the Phase 1b, the combination of ONV with either LDAC or DEC demonstrated safety, tolerability and preliminary efficacy. Biomarker positivity was observed in a subset of pts, possibly related to dependency of the tumor on PLK1 activity, and was associated with objective response. In addition, gene expression data suggest that biomarker positive pts have a worse prognosis and an underlying OXPHOS-dependency of the tumor. The OXPHOS-dependent AML population has been shown to be resistant to chemotherapy (Farge et al., Cancer Discov. 2017 Jul 1;7(7):716–35 ), therefore this hard-to treat population could potentially benefit from the addition of ONV.


Conclusion cited from the abstract: 

SA and COMBO olutasidenib has shown favorable safety and clinical activity in IDH1m R/R AML with a SA ORR of 41% (95% CI: 21, 64) and a COMBO ORR of 46% (27, 67), and durable disease control. Olutasidenib induces deep responses with IDH1 mutation clearance in a subset of treated pts. Phase 2 investigations of SA and COMBO olutasidenib at the RP2D are ongoing in multiple IDH1m AML populations. Additional combinations are also being explored.






Conclusion cited from the abstract:  In this phase 1 study of CC-90009, a first-in-class agent, evidence of deep GSPT1 degradation, on-target activity and promising antileukemic activity was observed. The observed TEAEs, in addition to those expected in this heavily pretreated R/R AML pt population, were generally well manageable. The study is ongoing with further optimization of dose, schedule and toxicity mitigation. Expansion cohorts in R/R AML and higher-risk myelodysplastic syndromes are planned.



Conclusion cited from the abstract: Taken together, here we have identified two potent small-molecule FTO inhibitor compounds (i.e., CS1 and CS2), effectively and selectively targeting FTO protein and showing potent therapeutic efficacy in treating leukemia.




Conclusion cited from the abstract: Blocking CD70/CD27-signaling and targeting CD70-expressing LSCs by the ADCC-optimized mAb, cusatuzumab, eliminated LSCs in vitro and in xenotransplantation experiments. In a phase 1 study promising activity of cusatuzumab in combination with HMA was observed in AML patients, in which translational data indicate that cusatuzumab selectively eliminates CD70-expressing LSCs.