A Phase 2 Trial of Enhancing Immune Checkpoint Blockade by Stereotactic Radiation and In Situ Virus Gene Therapy in Metastatic Triple-Negative Breast Cancer

Kai Sun, Yitian Xu, Licheng Zhang, Polly Niravath, Jorge Darcourt, Tejal Patel, Bin S. Teh, Andrew M. Farach, Carlo Guerrero, Sunil Mathur, Mark A. Sultenfuss, Nakul Gupta, Mary R. Schwartz, Susan L. Haley, Sindhu Nair, Xiaoxian Li, Thi Truc Anh Nguyen, Joseph D. Butner, Joe Ensor, Jaime A. MejiaZhuyong Mei, E. Brian Butler, Shu Hsia Chen, Eric H. Bernicker, Jenny C. Chang

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


PURPOSE: A Phase 2 trial of stereotactic radiotherapy and in situ cytotoxic virus therapy in patients with metastatic triple-negative breast cancer (mTNBC) followed by pembrolizumab (STOMP) was designed to evaluate dual approach of enhancing single-agent immune checkpoint blockade with adenovirus-mediated expression of herpes-simplex-virus thymidine-kinase (ADV/HSV-tk) plus valacyclovir gene therapy and stereotactic body radiotherapy (SBRT) in patients with mTNBC. PATIENTS AND METHODS: In this single-arm, open-label Phase 2 trial, patients with mTNBC were treated with ADV/HSV-tk [5 × 1011 virus particles (vp)] intratumoral injection, followed by SBRT to the injected tumor site, then pembrolizumab (200 mg, every 3 weeks). The primary endpoint was clinical benefit rate [CBR; complete response (CR), partial response (PR), or stable disease (SD) ≥ 24 weeks per RECIST version1.1 at non-irradiated site]. Secondary endpoints included duration on treatment (DoT), overall survival (OS), and safety. Exploratory endpoints included immune response to treatment assessed by correlative tissue and blood-based biomarkers. RESULTS: Twenty-eight patients were enrolled and treated. CBR was seen in 6 patients (21.4%), including 2 CR (7.1%), 1 PR (3.6%), and 3 SD (10.7%). Patients with clinical benefit had durable responses, with median DoT of 9.6 months and OS of 14.7 months. The median OS was 6.6 months in the total population. The combination was well tolerated. Correlative studies with Cytometry by Time of Flight (CyTOF) and imaging mass cytometry (IMC) revealed a significant increase of CD8 T cells in responders and of myeloid cells in non-responders. CONCLUSIONS: The median OS increased by more than 2-fold in patients with clinical benefit. The therapy is a well-tolerated treatment in heavily pretreated patients with mTNBC. Early detection of increased effector and effector memory CD8 T cells and myeloids correlate with response and non-response, respectively.

Original languageEnglish (US)
Pages (from-to)4392-4401
Number of pages10
JournalClinical cancer research : an official journal of the American Association for Cancer Research
Issue number20
StatePublished - Oct 14 2022


  • Antineoplastic Combined Chemotherapy Protocols/therapeutic use
  • Genetic Therapy
  • Humans
  • Immune Checkpoint Inhibitors
  • Radiosurgery
  • Thymidine/therapeutic use
  • Thymidine Kinase/genetics
  • Triple Negative Breast Neoplasms/drug therapy
  • Valacyclovir/therapeutic use

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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