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Prospective Dynamic BH3 Profiling for Clinical Use in Relapsed or Refractory AML

Award Number: R37CA304011
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2026
PERIOD OF PERFORMANCE END DATE: 08/31/2031

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Prospective Dynamic BH3 Profiling for Clinical Use in Relapsed or Refractory AML - Project Summary Disease recurrence is the leading cause of death for patients with acute myeloid leukemia. This is driven by the failure to achieve a second remission with available therapies. There is also limited guidance on how to select effective and avoid ineffective therapies, which are equally significant to patient outcome. Testing for targetable mutations is only relevant to 50% of patients that relapse and, even so, the majority of patients still do not achieve a complete remission with targeted single-agent therapies. Venetoclax is a BCL-2 inhibitor and priming agent that bolsters the effectiveness of drugs based on preclinical and clinical studies, but there is limited guidance on how to best partner therapies to leverage venetoclax-induced apoptosis. The overarching goal of this project is to improve the outcomes of patients with relapsed or refractory AML by using dynamic BH3 profiling to provide guidance on treatment selection for individual patients. This assay measures changes in apoptotic priming in leukemia cells after short ex vivo treatment. The dynamic BH3 profiling assay is a predictive biomarker for in vivo clinical response to venetoclax, targeted therapies and chemotherapy, but has not yet been tested prospectively for clinical use. Based on these recent data, dynamic BH3 profiling is hypothesized to predict response and nonresponse to therapies in patients with relapsed or refractory AML. The rationale for this project is that knowledge of feasibility and biomarker-guided therapeutic efficacy, and the associated patient-specific drug- induced mitochondrial sensitivities will set the stage for implementing functional biomarkers into AML clinical care, thereby providing new therapeutic opportunities. To define the clinical role and improve the prediction power of dynamic BH3 profiling, the following aims are proposed: In Aim 1, the role of dynamic BH3 profiling will be defined in a prospective phase 2 clinical trial of biomarker-guided therapy in patients with relapse or refractory AML. In this investigator-initiated trial, patients will undergo biomarker screening, which will guide them towards or away from venetoclax-based combination therapies available on trial. The co-primary objectives are determining the feasibility of performing the assay in real time and providing biomarker-guided treatment assignments, and the efficacy of biomarker-guided therapy (overall response rate). The secondary objectives are safety and long term clinical outcomes. Correlatives to evaluate for evidence of cytotoxicity among drugs with evidence of priming will be performed in parallel. In Aim 2, the detection of drug-induced apoptotic priming be comprehensively examined for opportunities to improve response prediction by intra-patient analyses with additional BH3 peptides and consideration of AML subpopulations including immature and mature blasts. Upon successful completion of the proposed research, these data will provide initial prospective clinical validation of the dynamic BH3 profiling assay. These contributions are expected to provide justification for its use in therapy- decision making, which will address the unmet therapeutic needs of AML patients and provide a starting point for its application in other cancers.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $388,616 )
2026	2026	DANA-FARBER CANCER INSTITUTE, INC.	450 BROOKLINE AVE	BOSTON	MA	02215	SUFFOLK	USA	Cancer Treatment Research	000	1	9/1/2026	NEW	$388,616
														Subtotal = $388,616

Grand Total All Awards = $388,616

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Prospective Dynamic BH3 Profiling for Clinical Use in Relapsed or Refractory AML

Award Number: R37CA304011

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/01/2026

PERIOD OF PERFORMANCE END DATE: 08/31/2031

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