# Development of a Phenotype-based Predictive Analytic for Acute Myeloid Leukemia

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2021 · $597,007

## Abstract

Project Summary
The 5-year overall survival from acute myeloid leukemia (AML) is less than 30%. While some patients are cured
with initial induction therapy, most patients relapse, and the expected outcomes in patients with relapsed and
refractory (R/R) AML are dismal. For this reason, developing methods to identify therapies likely to benefit R/R
AML patients is a top priority. This proposal aims to address critical unmet needs with a unique Academic-
Industry Partnership (AIP) between investigators at Vanderbilt University Medical Center, Karyopharm
Therapeutics, and Notable Labs. The BCL2 inhibitor, venetoclax (VEN), is transforming clinical practice for AML,
but activity in R/R AML is less pronounced, and resistance occurs in most patients. AIP investigators currenty
lead a multi-site investigator-sponsored study, testing VEN in combination with the selective inhibitor of nuclear
export (SINE) selinexor (SEL) in a Phase I trial for R/R AML (NCT03955783). This SEL/VEN trial grew from the
discovery that SEL synergizes with VEN and overcomes resistance mechanisms in some VEN-insensitive
patient samples. Given this, our AIP team has worked together to develop a precision medicine functional
platform for this novel combination in R/R AML. Notable Labs utilizes an automated high-throughput,
immunophenotype-based flow cytometry method to provide real time drug sensitivity data on multiple, specific
cell populations simultaneously within a given patient sample. Building from the only annotated cohort of patient
samples treated with SEL/VEN in the world, we propose to develop a precision medicine functional assay to
identify R/R AML patients most likely to benefit from SINE/VEN combination therapy. We will build, refine and
optimize the functional platform for SEL/VEN with samples from our current Phase I study and train the platform
on samples from the Phase 2 SEL/VEN clinical trial proposed by the AIP. Aim 1 will focus on determining assay
parameters specifically for SEL/VEN in R/R AML. Aim 2 will train the model with the phase II clinical trial of
SEL/VEN in R/R AML, and Aim 3 will contextualize the predictive analytic model on heterogenous genotypes
found in R/R AML. At the conclusion of this study, the functional medicine platform will be a companion
diagnostic ready for external validation which we will lead in a phase III efficacy trial of SEL/VEN in R/ R AML,
and serve as proof-of-principle for development of similar therapy-specifc precision medicine tools.

## Key facts

- **NIH application ID:** 10276293
- **Project number:** 1R01CA262287-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Tomer M Mark
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $597,007
- **Award type:** 1
- **Project period:** 2021-09-15 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10276293

## Citation

> US National Institutes of Health, RePORTER application 10276293, Development of a Phenotype-based Predictive Analytic for Acute Myeloid Leukemia (1R01CA262287-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10276293. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*