# Next Generation TOP1 Inhibition for the Treatment of Uterine Serous Carcinoma

> **NIH NIH P50** · MAYO CLINIC ROCHESTER · 2024 · $201,750

## Abstract

PROJECT SUMMARY – OVERALL
This revised application of the Mayo Clinic SPORE in Ovarian Cancer (OC) builds on translational research con-
ducted during Years 6-10 of funding. Our accomplishments over the past five years include i) identification of a
unique vaccine strategy that, in a phase I study, led to 39% recurrence free survival at 49 months in high grade
serous OC, ii) new understanding of the genomic and biochemical changes that limit the action of PARP
inhibitors (PARPis) in OC, iii) distribution of over 9600 biospecimens for OC research, and iv) publication of 220
articles. The Developmental Research Program (DRP) has contributed to two of the four projects in this renewal;
and the Career Enhancement Program (CEP) contributed to leadership of two projects. The overall goal of the
SPORE remains to support innovative, interactive, translational OC research that leverages the expertise of bas-
ic and translational investigators. This renewal contains four translational projects designed to investigate OC
biology and enhance therapeutic response, building on recent clinical advances and promising preclinical results:
• P1 (Development of a Th17-Inducing Dendritic Cell [DC] Vaccine for OC): Based on our study showing that
 DCs pulsed with Folate Receptor α peptides and matured to a Th17-inducing phenotype induced immune re-
 sponses in all patients and long-term recurrence-free survival in 39%, we will identify determinants of long-
 term vaccine response in a phase II trial and elucidate mechanisms of immune escape from this vaccine.
· P2 (Next Generation TOP1 Inhibition for the Treatment of OC): Building on our observation that TOP1 inhib-
 itors are active in PARPi-resistant OC models and this activity can be enhanced by PARPi treatment even in
 the face of PARPi resistance, this project will identify determinants of sensitivity to TOP1 inhibitor/PARPi
 combinations and conduct a phase II trial of the ultra-long acting TOP1i PLX038 with the PARPi rucaparib.
· P3 (Repurposing Ceritinib for OC Therapy): Based on the finding that ceritinib, a kinase inhibitor used for ALK-
 rearranged lung cancer, inhibits mitochondrial respiration, increases reactive oxygen species, and sensitizes
 OC cell lines and PDXs to PARPis independent of ALK status, we will identify pathways that mediate these
 effects and conduct a phase I trial of the ceritinib/olaparib combination.
· P4 (Treatment of Advanced OC Using Gene-Edited CAR NK Cells): Building on a prior developmental research
 project, this team located at the University of Minnesota will apply advanced cellular engineering techniques
 to generate activated NK cells with enhanced tumor homing and persistence, then test the safety and efficacy
 of administering this allogeneic adoptive immunotherapy in a phase I clinical trial in platinum-resistant OC.
These impactful projects are supported by four highly interactive cores: Core A (Administrative), Core B (Biospec-
imens/Patient Registry), Core C (Biosta...

## Key facts

- **NIH application ID:** 11126294
- **Project number:** 3P50CA136393-14S2
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** SCOTT H KAUFMANN
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $201,750
- **Award type:** 3
- **Project period:** 2009-07-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11126294

## Citation

> US National Institutes of Health, RePORTER application 11126294, Next Generation TOP1 Inhibition for the Treatment of Uterine Serous Carcinoma (3P50CA136393-14S2). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/11126294. Licensed CC0.

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