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
5519 - Is there a difference of Palliative care problems and needs between cancer and non-cancer hospitalized elderly patients?
Presenter: Ioanna Chatzi
Session: Poster Display session 1
Resources:
Abstract
2505 - There is a lack of clinical research for patients with cancer in palliative care
Presenter: Marie Vinches
Session: Poster Display session 1
Resources:
Abstract
5273 - Specialist Palliative Care (SPC) in Haematological Malignancy: Establishing practices in a UK Tertiary Cancer Centre (TCC)
Presenter: Emma Kedgley
Session: Poster Display session 1
Resources:
Abstract
5864 - Evaluation of the relationship between the attachment styles and psychological resilience of cancer patients receiving chemotherapy
Presenter: Fatma Bugdayci Basal
Session: Poster Display session 1
Resources:
Abstract
770 - Gefitinib along with Methotrexate as palliative therapy in PS 3 and above in metastatic squamous cell carcinoma head and neck cancer patients
Presenter: Vidya Dusi
Session: Poster Display session 1
Resources:
Abstract
4232 - High intensity end-of-life care in pediatrics, adolescent and young adult patients with cancer using an administrative database.
Presenter: Seiko Bun
Session: Poster Display session 1
Resources:
Abstract
4845 - Embedded outpatient palliative care service within the oncology clinic: Preliminary experience in Hacettepe Oncology Hospital
Presenter: Deniz Can Guven
Session: Poster Display session 1
Resources:
Abstract
3270 - Internet-based stepped care for individuals with cancer and concurrent anxiety or depression symptoms – results from a randomized controlled trial
Presenter: Birgitta Johansson
Session: Poster Display session 1
Resources:
Abstract
5503 - Impact of Cognitive-Behavioral-Therapy (CBT) on levels of anxiety, depression and distress in cancer patients (pts)
Presenter: Daniela Tregnago
Session: Poster Display session 1
Resources:
Abstract
5553 - Cytokine genetic variations and worse quality of life among family caregivers of head and neck cancer patients in palliative care
Presenter: Daniel Pequeno
Session: Poster Display session 1
Resources:
Abstract