1596TiPDUBLIN-3, a stage IIIb/IV NSCLC phase (Ph)3 trial comparing the plinabulin (P)/Docetaxel(D) combination with D Alone

AbstractBackgroundThe PD-L1 inhibitors Avelumab (AV) and Atezolizumab (AT) have proven clinical anticancer efficacy, however in NSCLC trials, Javelin Lung 200 (JAV for AV) failed, whereas OAK (for AT) met primary endpoint showing better survival vs 75  mg/m2 D as comparator. The authors suggested JAV trial design factors may have played a role (Barlesi, Lancet Oncology 2018). Firstly, its open-label study design lead to more D patients (pts) dropping out prior to receiving first D dose (8% vs 1% for D vs AV). Secondly, JAV did not stratify for region, resulting in 29% vs 25% Asian pts with D vs AV; Asian pts tend to respond better to D then non-Asians. However, tumor stage also might be another factor, since advanced primary and metastatic lesions likely harbor antigens (Ags) for which immune tolerance has already been developed. Mutation burden of advanced primary and metastatic lesions show high concordance (Sherwood, J Exp& Clin Canc Res 2015). In contrast, early or novel subclonal lesions located in the lung are more likely to harbor (novel) immunogenic Ags (De Bruin, Science 2014). More pts in JAV (close to 100% (6%M0) vs OAK (70.6%) were at stage IIIb/IV (Rittmeyer, Lancet 2016; OAK Team, 2019). P is a novel Dendritic Cell (DC) modulator that is combined with D. D induces Ags that DC cells can present to CD4 and CD8 T-Cells after P stimulation (Lloyd, AACR 2016). P has favorable safety/tolerability in  >  500 pts and prevents D-induced-Neutropenia (N) and -...
Source: Annals of Oncology - Category: Cancer & Oncology Source Type: research