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A phase II study of the oral selective AXL inhibitor bemcentinib with pembrolizumab in patients with advanced NSCLC
Krebs, Matthew G Helland, A. Costa, E. C. Aperribay, E. A. Gomez, M. D. Perez, J. T. Thompson, J. Strauss, J. Granados, A. L. O. Felip, E.
Krebs, Matthew G
Helland, A.
Costa, E. C.
Aperribay, E. A.
Gomez, M. D.
Perez, J. T.
Thompson, J.
Strauss, J.
Granados, A. L. O.
Felip, E.
Citations
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Abstract
Background: The RTK AXL is implicated in epithelial-to-mesenchymal
transition, negative regulation of anti-tumour immunity and resistance
to multiple therapies including immune checkpoint inhibitors. Bemcentinib
(BGB324) is a first-in-class, oral, highly selective and potent
AXL inhibitor which has been demonstrated to enhance anti-PD1
therapy. The combination of bemcentinib and pembrolizumab was
well tolerated and showed promising efficacy in previously treated IOnaïve
NSCLC patients (Cohort A, NCT03184571), particularly in those
with AXL positive disease, including PD-L1 negative patients. The
novel combination is now being assessed in patients refractory to
anti-PD-(L)1 therapy, considering the emerging need in this population
and AXL’s role as a mediator of resistance. Method: This is an
open-label, single-arm, 2-stage phase II study (Cohort B,
NCT03184571) to evaluate the safety and efficacy of bemcentinib
(200mg/d) in combination with pembrolizumab (200mg/q3wk) in
patients post anti-PD-(L)1 therapy. The primary endpoint is overall
response rate (ORR), and additional endpoints include efficacy by
biomarker expression, duration of response (DoR), disease control
rate (DCR), progression free survival (PFS), overall survival (OS),
and safety. Clinical efficacy endpoints are based on tumour imaging
evaluable by RECIST v1.1. Eligible patients received a maximum of
2 prior lines of therapy, with the most recent course having
included a PD-(L)1 inhibitor. To be eligible, patients must have
exhibited disease control (CR/PR/SD) for at least 6 months on prior
PD-(L)1 inhibitor therapy with disease progression occurring within
12 weeks since last dose. Bemcentinib will be administered as a
loading dose of 400mg on days 1, 2 and 3 followed by a dose of
200mg once daily. A fixed dose of 200 mg pembrolizumab will be
given by intravenous infusion over 30 minutes every 3 weeks.
Bemcentinib and pembrolizumab will be given until disease progression,
unacceptable dose toxicity, or for a maximum of 35 cycles.
Tumour specimens will be analysed for PD-L1 expression (22C3
pharmDx), AXL by IHC, and infiltrating immune cells. The prespecified
efficacy threshold for continuation into the second stage is
1 objective response among the first 13 patients, at which point up
to a further 16 patients may be evaluated, for a total of 29 patients.
Result: Section not applicable Conclusion: Section not applicable
Description
Date
2021
Publisher
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Keywords
Type
Meetings and Proceedings
Citation
Krebs M, Brunsvig P, Helland Å, Viñolas N, Aix S, Carcereny E, et al. P1.01-72 A Phase II Study of Selective AXL Inhibitor Bemcentinib and Pembrolizumab in Patients with NSCLC Refractory to Anti-PD(L)1. Journal of Thoracic Oncology. 2019 Oct;14(10):S388.