CHICAGO—Two agents targeting novel pathways in myeloid malignancies—mivebresib and bencentinib—are showing promise in early studies, according to a speaker at the 2018 ASCO Annual Meeting.
“Both BET and AXL inhibition appear to be new and exciting targets in myeloid malignancies,” said Alice S. Mims, MD, and both have produced responses as single agents.
Dr Mims, of Ohio State University Wexner Medical Center in Columbus, made these observations in a poster discussion presentation that included commentary on the two agents.
Mivebresib (ABBV-075), an inhibitor of bromodomain and extra terminal (BET) proteins, yielded some responses in relapsed/refractory acute myeloid leukemia (AML) patients in a first-in-human study presented at the meeting (abstract 7019*).
Bemcentinib (BGB324), a first-in class selective inhibitor of the AXL tyrosine kinase, also showed activity in preliminary results of a study including patients with relapsed/refractory disease (abstract 7020*).
“It will be important to know individual patient characteristics to determine the potential response predictors,” Dr Mims said.
Mivebresib is the subject of an ongoing phase 1 dose-escalation study in which 23 patients have been treated. That includes 12 who received the BET inhibitor as monotherapy, and 11 who got it in combination with the BCL-2 inhibitor venetoclax, which is indicated in CLL and has breakthrough therapy designation for AML.
Investigators observed responses in 3 of 17 evaluable patients (17.6%), including 1 complete remission with incomplete blood count recovery in a patient on mivebresib monotherapy, plus 1 partial response and 1 patient achieving a morphologic leukemia-free state with the combination.
The most common grade 3/4 treatment-emergent adverse events included anemia in 52%, thrombocytopenia in 44%, and febrile neutropenia in 26% of patients, with no dose-limiting toxicities noted as of this report.
Bemcentinib is being evaluated in a phase 1/2 trial including patients with relapsed/refractory AML and myelodysplastic syndromes (MDS).
For 32 patients treated so far, 3 patients achieved a complete remission, including 1 AML and 2 MDS patients.
In addition, 3 patients achieved partial response, including 1 MDS and 2 AML patients.
Treatment with bemcentinib was generally well-tolerated, and most adverse events were mild or moderate, investigators reported in their poster.
Pre-treatment levels of soluble AXL were lower in responders compared with non-responders, investigators also noted.
“Soluble AXL levels may be a predictive biomarker for AXL inhibition, but further assessment is necessary,” Dr Mims said.
*Data presented at the meeting differ from the abstracts.