Abstract PS16-01: Comparison of an Atezolizumab monotherapy window followed by Atezolizumab and chemotherapy vs. Atezolizumab and chemotherapy alone in triple negative breast cancer (TNBC) – final analysis of the neoadjuvant neoMono trial
Authors: Kolberg Hans-Christian , Schumacher Johannes , Erber Ramona , Braun Michael , Fasching Peter A. , Grischke Eva-Maria , Schem Christian , Lux Michael P. , Deryal Mustafa , Hoffmann Oliver , Heinrich Bernhard , Kunz Georg , Lübbe Kristina , Krabisch Petra , Hartmann Arndt , Raeth Philip , Kasimir-Bauer Sabine , Kolberg-Liedtke Cornelia 
Published: May 2024

Abstract
Background:
Improvement of systemic therapy of TNBC still is a medical need. Exploratory data from the neoadjuvant GeparNuevo trial suggested a benefit from an immune checkpoint inhibitor (ICI) monotherapy window in TNBC. The neoMono trial prospectively analyzed whether the addition of a preceding Atezolizumab monotherapy window prior to Atezolizumab and chemotherapy (CTX) improves pCR rates among patients (pts) with early TNBC. In an interim analysis after 100 pCR events, patients with unselected TNBC did not show a significant benefit from an Atezolizumab monotherapy window, while an exploratory analysis suggested a highly clinically relevant benefit among pts with PD-L1 positive TNBC. Here we present the final primary endpoint analysis.
Methods:
NeoMono is a phase 2 randomized multicenter trial that was planned to recruit a maximum of 458 female and male pts with primary TNBC (defined as ER/PR &lt; 10% and HER2 negative) with tumor stages cT1c – cT4d (cN0 and cN+). As the protocol mandated termination of trial recruitment based on the results of the interim analysis, the final ITT population was limited to 359 pts. PD-L1 status had to be identifiable by central pathology by means of the VENTANA PD-L1 (SP142) assay and was defined by PD-L1 expression on immune cells (IC). Neoadjuvant treatment in both study arms consisted of Atezolizumab 1200 mg every 3 weeks in addition to neoadjuvant CTX (12 x Carboplatin/Paclitaxel q1w followed by 4x Epirubicin/Cyclophosphamide q3w). Combination therapy in arm A was preceded by an Atezolizumab monotherapy window of 840 mg once two weeks prior to initiation of combination therapy, while patients in arm B received no immune monotherapy window.
Study goals are to compare the efficacy of neoadjuvant CTX + Atezolizumab with versus without a two-week atezolizumab monotherapy window preceding CTX + ICI (primary endpoint: pCR) and to identify biomarkers for response and resistance through analysis of sequential tissue and liquid biopsies. The neoMono statistical design uses Bayesian posterior probabilities (uniform prior distribution) and logistic regression to analyze the primary endpoint.
Results:
180 pts in arm A and 179 in arm B from 34 study sites were included in the final primary endpoint analysis. Demographics and baseline characteristics as well as drug exposure were well-balanced in both arms. Posterior mean pCR rates in the ITT population in study arms A and B were 65.7% (95% high posterior density interval (HPDI): 58.5%, 72.5%) and 69% (62.2%, 75.9%), respectively. In an exploratory analysis stratified by PD-L1 IC status (negative: &lt; 1% versus positive: ≥ 1%), pCR rates in arm A were 91.5% in the PD-L1 IC-positive group and 56.1% in the PD-L1 IC-negative group, the corresponding pCR rates in arm B were 82.2% and 64.5%, respectively. In a multivariate analysis of the ITT population including tumor size, nodal status, tumor grade, age and PD-L1 status, the odds ratio for achieving a pCR was 4.77 (p &lt; 0.001) for PD-L1-positive and 2.36 (p=0.023) for grade 3 tumors.
In an exploratory analysis including HER2 status, odds for achieving a pCR were significantly higher for patients with HER2-negative (IHC 0) vs. HER2-low tumors (OR 1.73, p=0.036).
No new safety signals were observed.
Conclusion:
The final primary endpoint analysis of the neoMono trial demonstrated the highest pCR rates ever reported in a phase II/III trial in TNBC. While a significant impact of an ICI monotherapy window on the pCR rate after combination of CTX + ICI in an unselected ITT population could not be demonstrated, neoMono indicates for the first time in a randomized prospective setting that patients with immune active TNBC might derive particular benefit from a preceding ICI monotherapy window. The results of the neoMono trial are mainly justifying the conduction of a confirmative trial in immune active TNBC. However, our results underscore the potential role of pre-therapeutic ICI monotherapy window as part of future therapeutic concepts in TNBC.
Citation Format: Hans-Christian Kolberg, Johannes Schumacher, Ramona Erber, Michael Braun, Peter A. Fasching, Eva-Maria Grischke, Christian Schem, Michael P. Lux, Mustafa Deryal, Oliver Hoffmann, Bernhard Heinrich, Georg Kunz, Kristina Lübbe, Petra Krabisch, Arndt Hartmann, Philip Raeth, Sabine Kasimir-Bauer, Cornelia Kolberg-Liedtke. Comparison of an Atezolizumab monotherapy window followed by Atezolizumab and chemotherapy vs. Atezolizumab and chemotherapy alone in triple negative breast cancer (TNBC) – final analysis of the neoadjuvant neoMono trial [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS16-01.