The HER2-targeted monoclonal antibody, trastuzumab (Tz), is standard of care (SOC) for breast cancer (BCa) patients (pts) with HER2 over-expressing (IHC 3+, OE) tumors and reduces recurrence by 50%. Tz may also have some efficacy in HER2 1-2+ by IHC (low expression, LE), but is not currently approved for these pts. LE patients are at increased risk for recurrence. We have previously shown that NeuVax(E75 peptide + GM-CSF), a HER2-targeted cancer vaccine, is safe, immunogenic, and has clinical efficacy, particularly in LE pts. We are conducting a phase II trial combining Tz and NeuVax to prevent BCa recurrence in HER2 LE pts. Given the known cardiac toxicity (tox) of Tz, there is concern that combination therapy may worsen this tox. Here, we present the initial safety data.
Disease-free, HLA-A2, A3, A24, or A26 + , HER2 LE BCa pts at high risk for recurrence were enrolled after SOC treatment and randomized to vaccine group (VG) receiving Tz and NeuVax or control group (CG) receiving Tz and GM-CSF only. Cardiac ejection fraction (EF) was assessed at baseline and serially throughout treatment. Tz dosing was 8mg/kg loading, then 6mg/kg every 3 weeks. Pts received 6 total inoculations of NeuVax or GM-CSF, one every 3 weeks starting with the third Tz infusion. Demographic and safety data were collected and analyzed with appropriate statistical tests.
In March 2016, the 150th pt was randomized triggering this pre-specified safety analysis (VG n = 81, CG n = 69). There were no significant differences in treatment factors. There were no related tox > grade 3 nor difference between treatment arms. There was no difference in EF over time (baseline (T0) to 6mo (T6)) between VG v CG (T0: 61.4 + 0.6%, T6: 60.5 + 0.9% v T0: 61.6 + 0.7%, T6: 60.7 + 1.0%, p = 0.9). There was 1 CG pt who experienced a grade 3 cardiac adverse event, but their EF returned to baseline after discontinuation of Tz.
This novel combination of Tz and NeuVax in HER2 LE pts is well tolerated and the cardiac effects of Tz are not impacted by the addition of NeuVax. We will continue to enroll in this ongoing trial, and will report immunologic and clinical outcomes in a planned interim analysis after 12 months follow-up.
Clinical trial identification
Legal entity responsible for the study
G. Choy: Senior Vice President of Clinical Sciences and Operations for Galena Biopharma. B. Nejadnik: Executive Vice President and Chief Medical Officer for Galena Biopharma. G.E. Peoples: Inventor rights to Neuvax (E75 + GM-CSF). Consultant for Galena Biopharma. All other authors have declared no conflicts of interest.