616. Acute Myeloid Leukemia: Novel Therapy, excluding Transplantation: Novel Targets and Combinations
Naval G. Daver, et al.
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.
Geoffrey L. Uy, et al.
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.
Rui Su, et al.
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.
Adrian F Ochsenbein, et al.
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.