Personalised Neoantigen-targeting Cancer Vaccine NECVAX-NEO1 in Neoadjuvant Triple-negative Breast Cancer

Phase I/II, multicenter, open-label, single-arm trial in triple-negative breast cancer patients under first-line neoadjuvant therapy with approved standard of care anti-PD-1 monoclonal antibody (PD-1 inhibitor), epirubicin/cyclophosphamide chemotherapy, and nab-paclitaxel therapy or SoC carboplatin/paclitaxel and epirubicin/cyclophosphamide or doxorubicin/cyclophosphamide chemotherapy. Optionally, NECVAX-NEO1 treatment in addition to standard of care anti-PD1 monoclonal antibody therapy can be prolonged after breast cancer surgery for another 24 weeks, according to the investigator's decision taking into consideration the study patient's health status. Personalized NECVAX-NEO1 constructs containing an eukaryotic expression plasmid encoding a series of selected neoantigen epitopes will be manufactured for administration as a patient-specific investigational medicinal product (IMP). The IMP will be administered and as an add-on therapy to the standard of care PD-1 inhibitor therapy. The trial will consist of mainly: Cohort 1 (n=8) * A Screening and Induction period of up to 12 weeks, including the neoantigen selection and manufacturing phase, and first-line treatment with PD-1 inhibitor therapy with epirubicin 90 mg/m2/cyclophosphamide 600 mg/m2 every 3 weeks combined with pembrolizumab 200 mg as standard of care treatment, * A Treatment period of up to 12 weeks with prime and booster administrations of NECVAX-NEO1 in addition to continuation of PD-1 inhibitor pembrolizumab 200 mg every 3 weeks and nab-paclitaxel 125 mg/m2 once a week for 12 weeks up to planned tumor surgery, * An optional prolongation of booster administration of NECVAX-NEO1 in addition to continuation of PD-1 inhibitor up to 24 weeks, and * A Follow-up period of 4 weeks, with an End of Treatment (EoT) visit at Week 16 or at Week 40 (in case of the optional treatment prolongation). * A long-term safety follow-up period (observation period) after EoT for up to 24 months. Cohort 2 (n=20) * A Screening and Induction period of up to 12 weeks, including the neoantigen selection and manufacturing phase, and first-line treatment with PD-1 inhibitor therapy with paclitaxel 80 mg/m2 once weekly/carboplatin on an area under the concentration-time curve of 5 mg per milliliter per minute once weekly over 12 weeks combined with pembrolizumab 200 mg as standard of care treatment, * A Treatment period of up to 12 weeks with prime and booster administrations of NECVAX-NEO1 in addition to continuation of PD-1 inhibitor pembrolizumab 200 mg every 3 weeks and epirubicin 90 mg/m2/cyclophosphamide 600 mg/m2 or doxorubicin 60 mg/m2/cyclophosphamide 600 mg/m2 for 12 weeks up to planned tumor surgery, * An optional prolongation of booster administration of NECVAX-NEO1 in addition to continuation of PD-1 inhibitor up to 24 weeks, and * A Follow-up period of 4 weeks, with an End of Treatment (EoT) visit at Week 16 or at Week 40 (in case of the optional treatment prolongation). * A long-term safety follow-up period (observation period) after EoT for up to 24 months.