Phase 2 trial of imprime and pembrolizumab immunotherapy in metastatic triple negative breast cancer patients who have progressed beyond first line chemotherapy
The Phase 2 IMPRIME 1 study evaluated the combination of the pathogen-associated molecular pattern (PAMP) Imprime with the immune checkpoint inhibitor (ICI) pembrolizumab as second or later line of treatment (2 L+) for patients with metastatic triple-negative breast cancer (mTNBC). Eligible patients with mTNBC received weekly Imprime (4 mg/kg) intravenously in combination with pembrolizumab (200 mg every 3 weeks). Primary endpoints were overall response rate (ORR) and safety. Secondary endpoints included disease control rate (DCR), duration of response (DoR), progression free survival (PFS), and overall survival (OS). Exploratory endpoints included correlations between immune cell activation markers in tumor tissues and blood and response to therapy. Of the 42 evaluable patients, six had a response (one complete, five partial), with an ORR of 14.3% by RECIST v1.1. Median PFS was 2.7 months, median OS was 16.4 months, and DCR was 54.8%, with responders achieving a median DoR of 15.2 months. Therapy was generally well tolerated and resulted in an increase of immune activation markers, with higher levels of activation in peripheral blood associated with response and improved survival. The combination of Imprime and pembrolizumab was safe and demonstrated immune activation in tumor tissues and peripheral blood in patients with TNBC. Improved response rates were observed compared to historical studies of ICI monotherapy in similar patient populations. Study number (ClinicalTrials.gov trial registration): NCT02981303.
Authors
- Virginia F. Borges (ORCID: https://orcid.org/0000-0003-1158-7524)
- Maysa Abu‐Khalaf (ORCID: https://orcid.org/0000-0003-4888-7547)
- B Osterwalder (ORCID: https://orcid.org/0009-0003-0333-6650)
- Paulette Mattson
- Nandita Bose (ORCID: https://orcid.org/0000-0002-9025-6805)
- Alison Stopeck (ORCID: https://orcid.org/0000-0003-4762-1392)
- Ben J. Harrison (ORCID: https://orcid.org/0000-0002-2226-2074)
- Anissa Chan (ORCID: https://orcid.org/0009-0002-3381-8960)
- Michele Gargano (ORCID: https://orcid.org/0000-0002-6659-8709)
- Michael Chisamore (ORCID: https://orcid.org/0009-0006-8629-8232)
- Bartosz Chmielowski (ORCID: https://orcid.org/0000-0002-2374-3320)
- Joyce O’Shaughnessy (ORCID: https://orcid.org/0000-0002-2955-5523)
- Ruta Rao (ORCID: https://orcid.org/0000-0003-3037-2318)
- Joanna Cox
- José Iglesias (ORCID: https://orcid.org/0000-0001-7851-0498)
- J. J. Graff
- Bin Xie (ORCID: https://orcid.org/0000-0002-8663-9336)
- Lida A. Mina (ORCID: https://orcid.org/0000-0003-2606-9922)
- Jeremy Drees
- Mark Uhlik
- Arkadiusz Z. Dudek (ORCID: https://orcid.org/0000-0002-9114-8945)
- Nadine Ottoson
- Xiaohong Qiu
Institutions
- Rush University Medical Center (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Thomas Jefferson University (US)
- Baylor University (US)
- University of California, Los Angeles (US)
- Texas Oncology (US)
- Baylor University Medical Center (US)
- Abbott (United States) (US)
- Swedish Medical Center (US)
- FuelCell Energy (United States) (US)
- Mayo Clinic in Arizona (US)
- BH Consulting (Ireland) (IE)
- University of Colorado Anschutz Medical Campus (US)
- Stony Brook University (US)
Publication Details
- Journal
- The Journal of Immunology
- Published
- 2025-05-08
- DOI
- https://doi.org/10.1093/jimmun/vkaf079
- Citations
- 1
- Primary Topic
- Cancer Immunotherapy and Biomarkers
- Type
- article
- Field-Weighted Citation Impact
- 1.05