637. Myelodysplastic Syndromes—Clinical Studies: Combination Therapies
Conclusion cited from the abstract:
Ven monotherapy and combination Ven+Aza were well tolerated in pts with R/R MDS and most AEs were manageable. Although the study is still ongoing, the 6-mos OS estimate of 57% in monotherapy pts compares favorably to historical controls. In addition, the ORR observed with combination therapy, and the observed 9-mos OS rate of 83% also compare favorably with historical data. Updated data on safety and efficacy, including data on RP2D, will be presented at the meeting.
Shyamala C. Navada, et al.
Conclusion cited from the abstract: The efficacy (90% ORR & 34% CR) and safety of oral rigosertib and AZA in combination is favorable as first line therapy in pts with HMA naïve HR MDS and are comparable to historical results for standard dose AZA monotherapy (ORR 38% and <20% CR). The transfusion independence (TI) of 30% in HR MDS pts is clinically meaningful and needs to be confirmed in a large randomized phase III study. Oral rigosertib in combination with AZA was well tolerated and has now been administered in repetitive cycles for more than two years. Rigosertib is attractive combination partner for AZA because of the oral formulation, non-overlapping toxicity, mechanism of action and synergy. Based on the efficacy results and favorable safety profile, a pivotal Phase III trial in higher-risk HMA naive MDS population is planned.
Conclusion cited from the abstract: CB-839 at a dose of 600 mg BID orally continuously daily is safe and well tolerated in combination with azacitidine in pts with advanced MDS with an acceptable safety profile. Preliminarily encouraging response rates include mCR/HI of 62.5%, including 100% in prior HMA exposure, 66.6% in TP53 and 83.3% in patients with complex karyotype. The trial continues to accrue. (NCT0347993)
Andrew H. Wei, et al.
Conclusion cited from the abstract: The combination therapy of Ven+Aza demonstrated a tolerable safety profile and promising efficacy in pts with HR-MDS. The maximum tolerated dose of Ven without dose-limiting toxicities was determined to be 400 mg in this HR-MDS population.
David A Sallman, et al.
Conclusion cited from the abstract: Magrolimab+AZA is a novel immunotherapy regimen that blocks a key macrophage checkpoint. The combination therapy continues to be well tolerated with robust activity in MDS and AML patients with an ORR of 100% and 69%, respectively. High rates of putative LSC eradication suggest potential durable responses, with no median duration of response yet reached. Initial data indicate that 5F9+AZA may be particularly effective in TP53 mutant patients, a treatment-refractory subgroup. Expansion cohorts are ongoing (NCT03248479) with registrational studies in MDS being initiated. Additional patients, follow-up, and mutational characterization will be reported at time of presentation. Funded by Forty Seven and the California Institute for Regenerative Medicine.
Uma Borate, et al.
Conclusion cited from the abstract:
In this ongoing study in patients with HR-MDS and AML, the combination of MBG453 and decitabine was safe and well tolerated, and exhibited evidence of anti-leukemic activity with encouraging preliminary response rates occurring at a median of 2 cycles, with durability in both HR-MDS and AML. These findings validate TIM-3 as a promising therapeutic target in MDS and AML and support further clinical development of MBG453 in combination with HMAs in patients with MDS and AML.