# Serial immunotherapy combination to modulate the tumor environment in patients with metastatic gastroesophageal cancer

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2022 · $639,268

## Abstract

PROJECT SUMMARY/ABSTRACT
Development of effective therapies is an urgent unmet medical need for patients with metastatic
gastroesophageal adenocarcinoma (mGEA). The advent of immune checkpoint inhibitors such as anti-
programmed death (PD)-1 antibodies has revolutionized treatment of some cancers but benefits only a
minority of patients with GEA. Combination approaches are required to extend this benefit to more patients.
Most studies of immunotherapy combinations in GEA initiate PD-1 blockade at the same time as cytotoxic
therapy despite the possibility that cytotoxic agents may kill some of the very T cells invigorated by PD-1
blockade, as our group and others have shown. Our long-term goal is to develop immunotherapy combinations
that avoid this problem through rational sequencing of immunotherapy with other anti-cancer agents to
enhance tumor destruction and improve patient survival. Based on our preliminary data, we hypothesize that
serial combination immunotherapy utilizing anti-PD-1 and anti-angiogenesis therapy with immunomodulatory
chemotherapy in a predefined sequence leads to meaningful improvements in clinical outcomes in association
with disruption of the immunosuppressive tumor microenvironment and promotion of antitumor systemic
immune responses. To test this hypothesis, we will perform a phase II trial to determine the therapeutic
efficacy of serial combination immunotherapy and examine its impact on local and systemic immune responses
in patients with mGEA through the following specific aims: Aim 1 will determine the therapeutic efficacy of
serial combination immunotherapy in patients with metastatic GEA. Aim 2 will interrogate patient samples
collected longitudinally from the parent trial to identify the impact of serial immunotherapy on
immunosuppressive, antitumor, and angiogenic components within the tumor environment, including tumor-
related local and systemic immune responses. Our expected outcomes are to show improved clinical efficacy
using an innovative immunotherapy combination in which PD-1 blockade is delivered in a predefined sequence
and to gain critical knowledge on the impact of this serial immunotherapy approach on tumor-related local and
systemic immune responses in patients with mGEA patients. Together, these new proof-of-concept data are
expected to inform the design of future definitive clinical trials that can improve the survival of patients with
immunotherapy-resistant metastatic GEA.

## Key facts

- **NIH application ID:** 10320947
- **Project number:** 5R01CA248147-02
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** Harry H Yoon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $639,268
- **Award type:** 5
- **Project period:** 2021-01-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320947

## Citation

> US National Institutes of Health, RePORTER application 10320947, Serial immunotherapy combination to modulate the tumor environment in patients with metastatic gastroesophageal cancer (5R01CA248147-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10320947. Licensed CC0.

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