Abstract 4125
Background
The 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 -Thrombocytopenia (Blayney, ASCO 2018; IASLC 2018; ESMO 2018). DUBLIN-3 may have avoided some of the JAV design limitations.
Trial design
DUBLIN-3 (NCT02504489), is a global, single-blinded (for pts) Ph3 study in EGFR wild-type, stage IIIb/IV NSCLC pts (target n = 554) stratified for region (Asia/non-Asia), and receiving 2nd- or 3rd-line systemic therapy with D+P or D in a 1:1 ratio. Key inclusion criteria are, pts must have at least one measurable lesion located in the lung, and have failed a prior platinum-based regimen. Prior PD1/PD-L1 use is allowed. Primary endpoint is OS. Key secondary endpoints are incidence of Gr 4 N, D dose modification due to N, QoL, ORR, PFS, and DoR. The first pre-specified Interim Analysis (IA) occurred at ∼150 events and a second IA at ∼ 300 events is projected for Q4 2019.
Clinical trial identification
BPI-2358-103 NCT02504489.
Editorial acknowledgement
Legal entity responsible for the study
BeyondSpring Pharmaceuticals, Inc.
Funding
BeyondSpring Pharmaceuticals, Inc.
Disclosure
R. Mohanlal: Leadership role, Travel / Accommodation / Expenses, Full / Part-time employment, Officer / Board of Directors: BeyondSpring Pharmaceuticals, Inc; Shareholder / Stockholder / Stock options: BeyondSpring, Inc. L. Huang: Leadership role, Travel / Accommodation / Expenses, Full / Part-time employment, Officer / Board of Directors: BeyondSpring Pharmaceuticals, Inc; Shareholder / Stockholder / Stock options: BeyondSpring, Inc.
Resources from the same session
5037 - CXCR4, CCR2 and CCR5 expression in subsets of tumor cells with stem and/or EMT features
Presenter: Olga Savelieva
Session: Poster Display session 1
Resources:
Abstract
5729 - Expression of mutant p53 affects cancer cell sensitivity to topotecan
Presenter: Rimma Mingaleeva
Session: Poster Display session 1
Resources:
Abstract
5725 - Breast cancer organoids a new tool for the prediction of drugs penetration and patient’outcome
Presenter: Giuseppina Roscigno
Session: Poster Display session 1
Resources:
Abstract
5680 - Aptamer-mediated exosomes detection for early breast cancer identification.
Presenter: Cristina Quintavalle
Session: Poster Display session 1
Resources:
Abstract
2460 - MicroRNA-181c promotes tamoxifen resistance in breast cancer cells via upregulation Akt/mTOR axis
Presenter: Alexander Scherbakov
Session: Poster Display session 1
Resources:
Abstract
3751 - Spatio-temporal separation of tumor infiltrating CD8+ T-cells and HER2/neu+ tumor cells in tumor-immune milieu of infiltrating ductal carcinoma of the breast
Presenter: Sandhya Sreedharan
Session: Poster Display session 1
Resources:
Abstract
4664 - Large genomic rearrangements in BRCA1 and BRCA2 genes in the Portuguese population.
Presenter: Joao Pinto
Session: Poster Display session 1
Resources:
Abstract
4611 - Non-BRCA1/2 hereditary breast and ovarian cancer: findings from a multidisciplinary program
Presenter: Ana Monteiro
Session: Poster Display session 1
Resources:
Abstract
5340 - Quantitative imaging and characterization of collagen patterns in high grade serous ovarian carcinoma (HGSOC)
Presenter: Ruby Huang
Session: Poster Display session 1
Resources:
Abstract
4209 - Semiquantitative assessment of vimentin expression in prostate cancer (PC)
Presenter: Marina Puchinskaya
Session: Poster Display session 1
Resources:
Abstract