# Targeted immunotherapy for relapsed/refractory Hodgkin lymphoma

> **NIH NIH P50** · BECKMAN RESEARCH INSTITUTE/CITY OF HOPE · 2021 · $320,777

## Abstract

Patients with high-risk relapsed/refractory Hodgkin lymphoma have only a 20-50% chance of cure. This project 
addresses this problem in 2 independent, but sequentially compatible clinical trials. In Specific Aim 1, we 
propose the NICE trial, a phase II study of response-adapted sequential therapy using nivolumab (NIVO) +/- 
ICE chemotherapy as second-line therapy following induction failure or early relapse. Patients who achieve a 
complete response (CR) after 12 weeks of the PD-1 inhibitor NIVO proceed directly to autologous 
hematopoietic cell transplantation (AHCT). We will combine NIVO with ICE chemotherapy for 6 more weeks in 
patients not in CR after 12 weeks of NIVO, or who have not achieved at least a partial response after 6 weeks 
of NIVO. This approach, utilizing an innovative PET response-adapted treatment sequence, is designed to 
increase the proportion of patients who are in CR at the time of AHCT, and is expected to spare those patients 
transplanted after NIVO alone, from the toxicity of additional chemotherapy. It also offers a unique opportunity 
to examine the effect of PD-1 inhibitors on the Hodgkin lymphoma tumor microenvironment, through extensive 
correlative studies of paired biopsies taken just prior to therapy and after the first 6 weeks of NIVO treatment. 
These studies include 1) microarray gene expression profiling to identify differentially expressed genes and 
pathways in the tumor microenvironment, as well as signatures that may be associated with response to 
treatment; 2) spatially mapping the density/distribution of different T-cell and macrophage subsets associated 
with response to therapy, using a 7-color multiplexed immunofluorescence spatial analysis imaging platform; 
and 3) CD25 and PD-1/PD-L1 immunohistochemistry;. Specific Aim 2 addresses the dilemma that, as the 
field advances, patients treated with upfront immunotherapy may experience relapsed or progressive disease 
that is more intractable, necessitating potent AHCT regimens that are agnostic to prior immunotherapies. We 
have developed at City of Hope, a 90Y-labeled anti-CD25 antibody immunoconjugate to augment BEAM AHCT 
conditioning. This aTac-BEAM regimen takes advantage of the susceptibility of Hodgkin lymphoma to 
radiation, and targets that radiation to the CD25 antigen found on many Reed-Sternberg cells and on activated 
T cells and Tregs in the tumor microenvironment. Preliminary data from our phase I trial (funded by NCI 
R21CA185875-02) indicates that the regimen is feasible, remarkably well tolerated, and has promising 
efficacy. In the phase II trial proposed here, the anti-lymphoma activity of the aTac-BEAM AHCT conditioning 
regimen will be assessed by 2-year progression-free survival. The two studies will accrue simultaneously, and 
patients may enroll in them both; we suspect that reactivating T cells with NIVO may increase CD25 
expression, amplifying the number of targets for aTac-BEAM. Patients will also include those referred...

## Key facts

- **NIH application ID:** 10242161
- **Project number:** 5P50CA107399-14
- **Recipient organization:** BECKMAN RESEARCH INSTITUTE/CITY OF HOPE
- **Principal Investigator:** ROBERT Wi CHEN
- **Activity code:** P50 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $320,777
- **Award type:** 5
- **Project period:** 2004-09-02 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10242161

## Citation

> US National Institutes of Health, RePORTER application 10242161, Targeted immunotherapy for relapsed/refractory Hodgkin lymphoma (5P50CA107399-14). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10242161. Licensed CC0.

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