Abstract PD11-03: PD11-03 Comparison of a mono Atezolizumab window followed by Atezolizumab and chemotherapy with Atezolizumab and chemotherapy in triple negative breast cancer – an interim analysis of the adaptive randomized neoadjuvant trial NeoMono
Authors: Kolberg Hans-Christian , Schumacher Johannes , Erber Ramona , Braun Michael , Heinrich Bernhard , Hoffmann Oliver , Fasching Peter A. , Kunz Georg , Lux Michael P. , Schem Christian , Grischke Eva-Maria , Deryal Mustafa , Lübbe Kristina , Hartmann Arndt , Kasimir-Bauer Sabine , Kolberg-Liedtke Cornelia 
Published: March 2023

Abstract
Introduction: Improvement of systemic treatment of TNBC represents an unmet medical need. Targeted therapy of regulatory immune pathways has become an important option in the treatment of many malignant diseases including breast cancer. Neodjuvant trials combining chemotherapy and checkpoint inhibitors (KEYNOTE-522 and IMpassion031) have demonstrated a meaningful benefit regarding pathological complete remission (pCR) for the addition of PD-1- or PD-L1-inhibitors to chemotherapy in patients with TNBC. In the KEYNOTE-522 trial, the addition of an immune checkpoint inhibitor (ICI) to neoadjuvant chemotherapy also had a beneficial impact on event-free survival even in patients who did not achieve a pCR. Of note, in the neoadjuvant GeparNuevo trial only those patients with TNBC who received a 2-week checkpoint inhibitor monotherapy window before the start of neoadjuvant chemotherapy in combination with checkpoint inhibition, achieved a significant pCR benefit from the addition of the PD-1 inhibitor Durvalumab to neoadjuvant chemotherapy alone. Methods: NeoMono is a phase 2 randomized multicenter trial recruiting male and female patients with primary TNBC (defined as ER/PR &lt; 10% and HER2 negative). Neoadjuvant treatment in Arm A and B consists of Atezolizumab 1200 mg every 3 weeks in addition to neoadjuvant chemotherapy (i.e., 12 x Carboplatin and Paclitaxel q1w followed by Epirubicin and Cyclophosphamide q3w). Combination therapy in arm A is preceded by an Atezolizumab monotherapy window (i.e., 840 mg Atezolizumab once two weeks prior to initiation of combination therapy). Study goals are to compare the efficacy of neoadjuvant chemotherapy with Atezolizumab with and without an Atezolizumab two-week monotherapy window (primary endpoint: pCR) and the identification of biomarkers predicting (early) response to or resistance against Atezolizumab. The extensive translational program of the neoMono trial aims at identifying these biomarkers on tumor and patient level through analysis of sequential tissue and liquid biopsies. The NeoMono statistical design adapts the idea of a proof-of-concept trial and uses Bayesian posterior and predictive probabilities for inference about the primary hypothesis. Up to 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. Results: The predefined number of 50 patients in each arm being evaluable for the primary endpoint pCR has been reached and the results of the first planned interim analysis will be presented at the meeting. Conclusion: The addition of an ICI to state of the art neoadjuvant chemotherapy has recently been established as a new standard of care in TNBC. NeoMono has the potential to answer the question if the beneficial effect of the ICI can be increased by a chemotherapy free ICI monotherapy window prior to a combination with neoadjuvant chemotherapy.
Citation Format: Hans-Christian Kolberg, Johannes Schumacher, Ramona Erber, Michael Braun, Bernhard Heinrich, Oliver Hoffmann, Peter A. Fasching, Georg Kunz, Michael P. Lux, Christian Schem, Eva-Maria Grischke, Mustafa Deryal, Kristina Lübbe, Arndt Hartmann, Sabine Kasimir-Bauer, Cornelia Kolberg-Liedtke. PD11-03 Comparison of a mono Atezolizumab window followed by Atezolizumab and chemotherapy with Atezolizumab and chemotherapy in triple negative breast cancer – an interim analysis of the adaptive randomized neoadjuvant trial NeoMono [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD11-03.