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
5437 - Salivary cytokines and oral mucosa cells apoptosis in patients during hematopoietic cell transplantation: possible relationship with oral mucositis
Presenter: Luciana Corrêa
Session: Poster Display session 1
Resources:
Abstract
1483 - A randomized trial of sodium alginate prevention of radiation-induced esophagitis in patients with locally advanced NSCLC receiving concurrent chemoradiotherapy: OLCSG1401
Presenter: Toshihide Yokoyama
Session: Poster Display session 1
Resources:
Abstract
2047 - Taste and smell alterations (TSAs) in patients (pts) with stage II-III colon cancer (CC): a pilot within the PROTECT study
Presenter: Jeroen Derksen
Session: Poster Display session 1
Resources:
Abstract
5984 - Clinical characteristics are associated with acupuncture treatment response for xerostomia in cancer patients
Presenter: Wenli Liu
Session: Poster Display session 1
Resources:
Abstract
2845 - Psychosocial Distress of Adolescent and Young Adults with Cancer at Diagnosis: A Case-Matched Retrospective Cohort of 2045 Patients in British Columbia.
Presenter: Alannah Smrke
Session: Poster Display session 1
Resources:
Abstract
724 - Accuracy of distress thermometer to measure cancer-related mood disorders in Chinese patients with cancer
Presenter: Sudip Thapa
Session: Poster Display session 1
Resources:
Abstract
2357 - Modalities of biosimilar filgrastim use in clinical practice in >1000 patients receiving chemotherapy regimens with a rest period of ≤14 days: the TOPAZE study
Presenter: Jean Marc Phelip
Session: Poster Display session 1
Resources:
Abstract
1426 - The Effect of Increasing Doses of Pegfilgrastim (Peg) on Thrombocytopenia (T) in Breast Cancer (BC) Patients (pts) Receiving Taxotere (Doc), Doxorubicin, Cyclophosphamide (TAC) and Plinabulin (Plin)
Presenter: Douglas Blayney
Session: Poster Display session 1
Resources:
Abstract
712 - The use of intravenous ferric carboxymaltose without erythropoiesis-stimulating agents in the treatment of anemia in cancer patients undergoing chemotherapy with or without radiotherapy
Presenter: Hikmat Abdel-Razeq
Session: Poster Display session 1
Resources:
Abstract
1496 - Randomized, double-blind, cross-over Phase I study comparing pharmacokinetics, pharmacodynamics, safety and immunogenicity of a biosimilar pegfilgrastim with EU and US references
Presenter: Maria Velinova
Session: Poster Display session 1
Resources:
Abstract