A Pilot Study of Neoadjuvant Nivolumab, Ipilimumab and Intralesional Oncolytic Virotherapy for HER2-Negative Breast Cancer

This study was a single arm phase 1 trial that assessed the regimen safety and feasibility as well as tumor response in patients with localized HER2-negative breast cancer treated with talimogene laherparepvec (T-VEC) in combination with nivolumab and ipilimumab. The primary objective was to evaluate the safety and adverse event profile of this treatment combination. Six patients were enrolled, four having relapses after prior neoadjuvant chemotherapy, and two who were previously untreated. One patient had a pathological complete response, three patients had pathological partial responses, one showed no significant response, and one had disease progression. Biopsies demonstrated increased immune cell infiltration in samples from patients who responded to therapy. In this study, the checkpoint blockade immunotherapy combined with T-VEC provided responses in patients with advanced or relapsed HER2-negative breast cancer at the expense of long-term toxicities.]]>
Study inclusion: Patients 18 years of age or older with pathologically proven, palpable, and injectable localized HER2-negative invasive breast carcinoma with a diameter of 1.0 cm or more. If patients had received prior neoadjuvant chemotherapy, they had to have full recovery from the acute toxic effects with suitable hematologic, renal, and liver function and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.Study exclusion: History of malignancies, except cured basal cell carcinoma, cutaneous squamous cell carcinoma, melanoma in situ, superficial bladder cancer or carcinoma in situ of the cervix.Prior exposure to any anti-PD-1 or anti-PD-L1 antibody, or any anti-CTLA 4 antibodies. Not have received prior treatment with T-VEC or other oncolytic virus agents. Not have an active infection requiring systemic therapy, nor a viral infection requiring intermittent treatment with an antiherpetic drug. Patients must not have received any live vaccine within 30 days prior to registration. Patient must not have evidence of any clinically significant immunosuppression such as the following: primary immunodeficiency state such as severe combined immunodeficiency disease; concurrent opportunistic infection; receiving systemic immunosuppressive therapy within 28 days before enrollment with the exceptions of intranasal, topical, and inhaled corticosteroids or oral corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent.Active or prior documented inflammatory bowel disease. Patients must not have known history HIV, hepatitis B, or hepatitis C. Active or prior documented autoimmune disease within the past 3 years. Evidence of an active herpetic infection and in patients who require daily antiviral therapy such as acyclovir. Any concurrent chemotherapy, immunotherapy, biologic or hormonal therapy for cancer treatment. Concurrent enrollment in another clinical study, unless it is an observational (non-interventional). History of (non-infectious) ILD/pneumonitis that required steroids or has current ILD/pneumonitis or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. ]]>