An adaptive randomized neoadjuvant two arm trial in triple-negative breast cancer (TNBC) comparing a mono Atezolizumab window followed by Atezolizumab - CTX therapy with Atezolizumab - CTX therapy (neoMono)

Background Improvement of systemic treatment of TNBC represents an unmet medical need. Recently, targeted therapy of regulatory immune pathways has become an important option in the treatment of numerous malignancies. Neodjuvant trials combining chemotherapy and checkpoint inhibitors (KEYNOTE-522 and IMPASSION-031) have demonstrated a meaningful benefit regarding pathological complete remission (pCR) for the addition of PD-1- and PD-L1-inhibitors to chemotherapy. In the neoadjuvant GeparNuevo trial only the subgroup of patients receiving a checkpoint inhibitor monotherapy window before the start of neodjuvant therapy achieved a pCR-benefit compared to neoadjuvant chemotherapy.

Methods NeoMono is a phase 2 randomized multicenter clinical trial recruiting patients with primary TNBC (defined as ER/PR 0 - < 10 % and HER2 negative). Neoadjuvant treatment consists of Atezolizumab 840 mg for two weeks in Arm A (Atezolizumab mono window). In arms A & B patients are then treated with Atezolizumab 1200 mg every 3 weeks plus 12 x Carboplatin and Paclitaxel q1w followed by Epirubicin and Cyclophosphamide q3w. Study goals are the comparison of efficacy of neoadjuvant chemotherapy with Atezolizumab with and without Atezolizumab two-week window (primary endpoint: pCR) and the identification of biomarkers predicting (early) response to or resistance against Atezolizumab. The neoMono statistical design adapts the idea of a proof-of-concept trial and uses Bayesian posterior and predictive probabilities for interference about the primary hypothesis. Four planned efficacy interim analyses provide decision points for early stopping for success or futility. The expected maximum number of patients to be recruited is 458.

Sponsor palleos healthcare

Trial information EudraCT-Number 2020-001651-40.

Interessenkonflikt

Johannes Schumacher, Angestellter des Sponsors palleos healthcare Cornelia Kolberg-Liedtke, Angestellte des Sponsors palleos healthcare.

Publication History

Article published online:
01 June 2021