# Molecular Characterization Trial

> **NIH NIH U54** · CLEVELAND CLINIC LERNER COM-CWRU · 2024 · $252,637

## Abstract

PROJECT SUMMARY
Molecular Characterization Trial
Navigating Extended Specimen Surveys for Therapeutic Selection (ROBIN-NESSTS)
Summary: Approximately half of all cancer patients are treated with radiation in the course of their disease.
There exists an opportunity and urgent need to apply new biological knowledge in the optimization of radiation
treatment and its combination with emerging targeted anti-neoplastic agents. At the core of the CCF/Emory
ROBIN U54 Center is a branched Molecular Characterization Trial (MCT) focused on longitudinal collection of
biospecimens and multimodal data from patients with muscle invasive bladder cancer (MIBC) and head and
neck squamous cell carcinoma (HNSCC) prior to-, during, and after radiotherapy. These molecular
characterization cohorts have been designed to incorporate immunomodulatory combination therapies as well
as standard-of-care chemoradiotherapy, aiming to address pressing translational questions by integrating
these trials throughout the ROBIN Center’s cores and projects. These are immune radiobiology-centered
“small N, high-content” study cohorts that will allow us to address critical knowledge gaps related to the
biological basis responses to combined modality radiotherapy. The central hypothesis being tested is that the
longitudinal collection of clinically annotated biospecimens and multimodal data from patients treated prior to,
during, and after radiotherapy from MCT cohorts examining radiation-based immunotherapies and standard of
care chemoradiation will provide new insights into the genetic, immunologic, and evolutionary basis of
therapeutic response. The ability to interrogate key questions across two distinct cancers will amplify our
capacity to identify generalizable molecular mechanisms underlying radiation resistance and
immunomodulatory activity. Our Specific Aims are to conduct a specimen collection and characterization trial
with 2 cohorts: (1) (MCTa): Adaptive RADiation therapy with concurrent Sacituzumab Govitecan (RAD-SG) for
bladder preservation in patients with MIBC and (2) a Phase II trial of IMRT re-irradiation plus concurrent and
adjuvant nivolumab. The same sample and data acquisition will be obtained from two parallel cohorts of
standard of care cisplatin plus RT treated patients (n=20 for each site). The overarching objective of the high-
content study cohorts in this MCT is to rigorously dissect common mechanisms and drivers of efficacy and
resistance to the most promising radiation-based combinations in two cancers. We will address knowledge
gaps related to the genetic, immunologic, and molecular evolutionary basis of response to immunomodulatory
combination therapies by seamlessly integrating multi-modal data from these clinical cohorts across the
ROBIN Center’s laboratories, projects, and cores.

## Key facts

- **NIH application ID:** 10896481
- **Project number:** 5U54CA274513-03
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Omar Y Mian
- **Activity code:** U54 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $252,637
- **Award type:** 5
- **Project period:** 2022-09-14 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896481

## Citation

> US National Institutes of Health, RePORTER application 10896481, Molecular Characterization Trial (5U54CA274513-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10896481. Licensed CC0.

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