An Open-Label Study of Subcutaneous CpG ODN (PF03512676) in Combination with Trastuzumab in Patients with Metastatic HER2+ Breast Cancer - Article Summary

Sep 21, 2026

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CpG ODN is a Toll-like receptor 9 agonist with immunotherapeutic potential for aggressive breast cancers. This single-arm, open-label phase II trial evaluated the efficacy and safety of weekly subcutaneous CpG ODN with trastuzumab in six patients with advanced/metastatic HER2-positive breast cancer. Fifty percent achieved stable disease; median PFS was 8.3 months. Three participants stopped due to tolerability issues. Immune profiling showed increased VEGF-D at week 2 and higher monocytic MDSC and PD-1+ T cells in progressive disease, while NK cells were unchanged.

LanguageEnglish

CategoryResearch & Report

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Pages15

Reading Time38 min

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Abstract

Objectives

Methods

Results

Conclusions

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What did the researchers find?

What do the findings mean?

| An Open-Label Study of Subcutaneous CpGOligodeoxynucleotide (PF03512676) in Combination with Trastuzumab in Patients with Metastatic HER2+ Breast Cancer | Cancer Control Volume 31: 1–15
© The Author(s) 2024
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[DOI: 10.1177/10732748241250189](DOI: 10.1177/10732748241250189)[ ](DOI: 10.1177/10732748241250189)[journals.sagepub.com/home/ccx](journals.sagepub.com/home/ccx)

| | --- | --- | | Dionisia Quiroga, DO, PhD 1,2 􀀁, Robert Wesolowski, MD1,2, Sara Zelinskas, BS 1, Ashley Pinette, MD3,4, Brooke Benner, PhD 1, Emily Schwarz, BS 1,
Himanshu Savardekar, BS 1, Courtney Johnson, DO3,4, Andrew Stiff, MD, PhD 1,2, Lianbo Yu, PhD5, Erin Macrae, MD2,6, Maryam Lustberg, MD, MPH2,7, Ewa Mrozek, MD2,8, Bhuvaneswari Ramaswamy, MD2, and William E. Carson III, MD 1,3
Abstract
Objectives: CpG ODN is a Toll-like receptor 9 agonist with immunotherapeutic potential for many cancer types, including aggressive breast cancers. There is strong interest in utilizing CpG ODN as an adjuvant to improve clinical efﬁcacy of current treatments and immunogenicity of breast cancers not traditionally responsive to active immunotherapy, such as those that are human epidermal growth factor receptor 2 (HER2)-positive. This study aimed to study the efﬁcacy and safety of combination CpG ODN plus anti-HER2 antibody trastuzumab treatment in patients with advanced/metastatic breast cancer.
Methods: This single-arm, open-label phase II clinical trial treated patients (n = 6) with advanced/metastatic HER2-positive breast cancer with weekly subcutaneous CpG ODN and trastuzumab. Patients may have received any number of prior therapies to be enrolled (most enrolled at median 1 prior line of chemotherapy). Peripheral blood was collected at baseline and weeks 2, 6, 12, and 18 for immune analyses. Six patients were enrolled and 50% achieved stable disease (SD) response.
Results: Median PFS was 8.3 months. Three of the six patients enrolled opted to stop treatment due to tolerability issues. Multiplex assay for cytokine measurements revealed signiﬁcantly higher VEGF-D levels at week 2 compared to baseline. Peripheral blood mononuclear cells analyzed by ﬂow cytometry showed a signiﬁcant increase in monocytic MDSC between weeks 6 and 12. Patients with progressive disease tended to have higher levels of week 6 monocytic MDSC and PD-1+ T cells than patients with SD. NK cell populations did not signiﬁcantly change throughout treatment.
Conclusions: CpG ODN and trastuzumab treatment of metastatic HER2 + breast cancer was safe but was not tolerable for all patients. This combination did induce potentially predictive immune proﬁle changes in treated patients with metastatic HER2 + breast cancer, the signiﬁcance of which needs to be further explored. | | | 1 Pelotonia Institute for Immuno-Oncology, The James Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA 2Department of Internal Medicine, Division of Medical Oncology, The Ohio State University, Columbus, OH, USA
3Department of Surgery, The Ohio State University, Columbus, OH, USA 4Miami Valley Hospital, Dayton, OH, USA
5Center for Biostatistics, The Ohio State University, Columbus, OH, USA 6Columbus Oncology Associates, Columbus, OH, USA
7Yale School of Medicine, New Haven, CN, USA 8St. Rita’s Cancer Center, Lima, OH, USA
Corresponding Author:
William E. Carson, III, MD Department of Surgery The Ohio State University N924 Doan Hall 410 W. 10th Avenue Columbus, OH 43210, USA. Email: wi[lliam.carson@osumc.edu](lliam.carson@osumc.edu) | | Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ([https://creativecommons.org/licenses/by-nc/4.0/](https://creativecommons.org/licenses/by-nc/4.0/)) which permits non-commercial use, reproduction and distribution of the work wit

FAQs

What was the purpose of this study?

To assess the efficacy and safety of combining subcutaneous CpG ODN with trastuzumab in patients with advanced/metastatic HER2+ breast cancer and to evaluate immune effects.

How was the trial conducted and who participated?

This was a single-arm, open-label phase II trial with six patients treated weekly with subcutaneous CpG ODN plus trastuzumab.

What were the key findings for disease control, safety, and immune markers?

Fifty percent achieved stable disease and median PFS was 8.3 months. Treatment was not tolerable for all patients, with three stopping due to tolerability issues. Immune analyses showed higher VEGF-D at week 2 and increased monocytic MDSC (and PD-1+ T cells in progressive disease), while NK cells did not significantly change.

Sep 21, 2026

Uploaded by Hazel