Thursday, November 21, 2024 11/21/2024

Minority PDX Development and Trial Center: Baylor College of Medicine and MD Anderson Cancer Center Collaboration on Mechanistic Studies to Dissect and Combat Health Disparities in Cancer

Award Number: U54CA233223
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: COOPERATIVE AGREEMENT
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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1 This application is being submitted in response to the Notice of Special Interest (NOSI) 2 identified as NOT-CA-22-039. Triple negative breast cancer (TNBC) is a biologically 3 heterogeneous and clinically important breast cancer subtype because if it were considered a 4 distinct disease, TNBC would rank as the 5th leading cause of cancer deaths in women. TNBC 5 also is more prevalent in younger premenopausal women especially Black or African Americans. 6 Protein translational regulation has been demonstrated to be a potential vulnerability in cancer 7 including TNBC. The eIF4A RNA helicase is a key regulator of translation initiation as part of the 8 eIF4F translation initiation complex. Interestingly, eIF4A selectively inhibits the translation of many 9 oncogene and growth factor mRNAs with highly structured 5’UTRs and is an essential gene in 10 many cancer cell lines. eFFECTOR Therapeutics has developed an improved eIF4A inhibitor, 11 Zotatifin (eFT226), that is currently being evaluated in a Phase I clinical trial (NCT04092673) in 12 patients with advanced solid tumor malignancies. In collaboration with eFFECTOR, we have 13 performed studies to determine the efficacy of Zotatifin in syngeneic genetically engineered 14 mouse (GEM) TNBC models developed in our laboratory. In these models a marked improvement 15 in tumor regression and time to end point was observed following combination treatment of 16 Zotatifin with standard-of-care either carboplatin or docetaxel. We now propose to expand these 17 studies to a series of racially and ethnically diverse TNBC PDX models with a special focus on 18 those derived from underserved populations in order to better identify which patients might benefit 19 from combination therapy in future clinical trials. Analysis of eIF4A protein expression across 20 TNBC PDX models has identified models with markedly different levels of Zotatifin target 21 expression. We now propose to optimize and elucidate mechanisms of single agent and 22 combination therapy with Zotatifin and chemotherapy across several high and low eIF4A PDX 23 models and to develop biomarkers to predict response. Our previous studies in GEM models 24 identified changes in the myeloid immune microenvironment including decreased infiltration of 25 neutrophils and repolarization of tumor associated macrophages to a less immunosuppressive 26 and more tumor inhibitory phenotype. Thus, we will also study effects of Zotatifin and 27 chemotherapy on circulating and tumor associated myeloid cells in these PDX models. In 28 summary, these preclinical studies may help provide key information to inform the design of future 29 clinical trials. Although these studies are initially focused on TNBC they may have a broader 30 application to other solid 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: 2025 ( Subtotal = -$291,184 )
2025	2022	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	1	10/1/2024	SUPPLEMENT FOR EXPANSION	-$291,184
														Subtotal = -$291,184

Issue Date FY: 2024 ( Subtotal = $0 )
2024	2022	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	008	1	7/10/2024	SUPPLEMENT FOR EXPANSION	$200,000
2024	2022	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	004	1	7/8/2024	SUPPLEMENT FOR EXPANSION	-$200,000
2024	2021	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	007	1	7/10/2024	SUPPLEMENT FOR EXPANSION	$120,000
2024	2021	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	003	1	7/8/2024	SUPPLEMENT FOR EXPANSION	-$120,000
2024	2019	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	002	1	7/8/2024	SUPPLEMENT FOR EXPANSION	-$291,184
2024	2019	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	006	1	7/10/2024	SUPPLEMENT FOR EXPANSION	$291,184
2024	2018	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	005	1	7/10/2024	NEW	$661,192
2024	2018	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	009	1	9/17/2024	NEW	$0
2024	2018	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	001	1	7/8/2024	NEW	-$661,192
2024	2018	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	1	11/1/2023	NEW	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $200,000 )
2022	2022	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	1	7/21/2022	SUPPLEMENT FOR EXPANSION	$200,000
2022	2018	BAYLOR COLLEGE OF MEDICINE	1 BAYLOR PLZ	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	001	1	8/30/2022	NEW	$0
														Subtotal = $200,000

Issue Date FY: 2021 ( Subtotal = $120,000 )
2021	2021	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	1	8/6/2021	SUPPLEMENT FOR EXPANSION	$120,000
														Subtotal = $120,000

Issue Date FY: 2019 ( Subtotal = $291,184 )
2019	2019	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	001	1	9/4/2019	SUPPLEMENT FOR EXPANSION	$291,184
2019	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	1	5/10/2019	NEW	$0
														Subtotal = $291,184

Issue Date FY: 2018 ( Subtotal = $6,353,982 )
2018	2018	BAYLOR COLLEGE OF MEDICINE	ONE BAYLOR PLAZA	HOUSTON	TX	77030	HARRIS	USA	21st Century Cures Act - Beau Biden Cancer Moonshot	000	1	9/20/2018	NEW	$6,353,982
														Subtotal = $6,353,982

Grand Total All Awards = $6,673,982

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Minority PDX Development and Trial Center: Baylor College of Medicine and MD Anderson Cancer Center Collaboration on Mechanistic Studies to Dissect and Combat Health Disparities in Cancer

Award Number: U54CA233223

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: COOPERATIVE AGREEMENT

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

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