Moffitt Cancer Center is the first center investigating the use of an oncolytic virus—a modified form of the herpes simplex 1 virus called talimogene laherparepvec (T-VEC)—to treat early-stage, triple negative breast cancer (TNBC). While the herpes virus is only FDA approved for melanoma treatment, Moffitt’s Breast Oncology Program is conducting the first-ever T-VEC trials—preliminary phase 1 data has been presented and recruitment is ongoing for Phase 2. Researchers are working to determine if injecting the virus directly into the tumor during chemotherapy and before surgery can help to eliminate triple negative breast cancer tumors.
T-VEC is a modified herpes simplex 1 virus that can specifically destroy cancer cells while leaving normal cells alone. It is directly injected into the tumor and works by killing cancer cells in two ways: by directly causing cancer cells to burst and by activating the immune system to attack tumors. The natural herpes simplex 1 virus typically causes cold sores around the mouth, but the talimogene laherparepvec version of the herpes virus has been genetically modified to prevent it from reproducing in normal tissue.
Results from the Phase 1 Trial of talimogene laherparepvec combined with neoadjuvant chemotherapy for non-metastatic triple negative breast cancer were presented at the 2019 AACR Annual Meeting. 1
Researchers hypothesized that use of T-VEC during neoadjuvant chemotherapy could improve pathologic complete response (pCR) rates through tumor cell lysis and recruitment of a robust immune response.
Led by Medical Director of the Clinical Trials Office and oncologist Dr. Hatem Soliman, this small early-phase 1 trial found that the addition of T-VEC to neoadjuvant chemotherapy was feasible at full FDA approved dose with manageable toxicity for patients with TNBC. The regimen also showed promising efficacy. The combination proved to be highly active in TNBC with an increase in pCR rate (55%) over expected rate of 30% with neoadjuvant chemotherapy alone. Preliminary evidence of robust immune activation was observed.
The study included 9 patients with TNBC. Patients were treated with paclitaxel, given weekly for 12 weeks, along with 5 doses of T-VEC at several dose levels given at weeks 1, 4, 6, 8, and 10 of the paclitaxel therapy. Patients then received doxorubicin and cyclophosphamide. Five of 9 patients with large TNBC tumors treated with T-VEC plus neoadjuvant chemotherapy achieved pCR. The remaining 4 patients in the trial had only small residual foci. pCr was defined as no invasive disease in the breast or lymph nodes.
"Even in the patients with residual disease, they had almost complete obliteration of their tumors as well,” Soliman said. “Incorporation of T-VEC into neoadjuvant chemotherapy for TNBC is feasible at full FDA-approved doses.” No dose-limiting toxicities were observed during the study.
This combination will continue to be evaluated in the ongoing phase II trial. Soliman noted that this trial is ongoing and actively recruiting patients to further evaluate the regimen’s efficacy. “We are seeing some impressive early results and hope to expand the use of T-VEC in the treatment of high-risk breast cancers in the near future.”
If you are interested in learning more about the breast cancer studies at Moffitt, call 1-800-679-0775 or complete a clinical trials inquiry form.
Reference: 1. Soliman H, Hogue D, Han H, et al. A Phase I trial of talimogene laherparepvec combined with neoadjuvant chemotherapy for non-metastatic triple negative breast cancer. Presented at: 2019 AACR Annual Meeting; March 29 to April 3, 2019; Atlanta, GA. Abstract CT040.