Abstract 2808
Background
The B-cell receptor (BCR) signaling pathway plays a central role in the development and survival of several subtypes of non-Hodgkin’s lymphomas (NHL). Despite available agents targeting the BCR pathway, no agents are yet curative, remissions are often short, there continues to be a need for more effective and less toxic therapies in the relapsed/refractory setting HMPL-523 is a selective small molecule inhibitor of the spleen tyrosine kinase (SYK), one of the key kinases of the BCR pathway. There are currently 3 ongoing international clinical studies with HMPL-523, including the present study being conducted in the United States (US), Italy, Poland, and Spain. Preliminary data demonstrate HMPL-523 has promising efficacy in multiple subtypes of lymphoma, with a favorable safety profile. We present here a trial-in-progress description of the ongoing US/EU trial, a phase 1 study that includes a dose-escalation and a dose expansion stage.
Trial design
Study Population: The target population is adult patients with histologically confirmed relapsed or refractory HL or NHL. To be eligible for enrollment, patients (pts) must have exhausted all approved therapy options available. Objectives: The primary objective is to assess the safety and tolerability of HMPL-523 in pts with relapsed or refractory lymphoma and to determine the maximum-tolerated dose (MTD)/ recommended phase 2 dose (RP2D). Preliminary efficacy in pts with relapsed or refractory lymphoma will be evaluated as a secondary objective in the dose expansion stage. Study Design: Dose-escalation will follow a 3 + 3 design and enroll 6 to 30 pts until the MTD/RP2D is reached. The proposed doses are 100 (1 pt only), 200, 400, 600, and 800 mg, daily in 28-day cycles, administered until disease progression, intolerable toxicity, no further benefit from study treatment, withdrawal, end of study, or death. Expansion stage will further evaluate the MTD/RP2D in ∼50 pts, with ∼10 pts in each cohort of: - Chronic lymphocytic leukemia/small lymphocytic lymphoma,
Mantle cell lymphoma,
Follicular lymphoma,
Marginal zone lymphoma, and
Waldenström’s macroglobulinemia/ lymphoplasmacytic lymphoma
Clinical trial identification
NCT03779113.
Editorial acknowledgement
Hoang-Lan Nguyen, Hutchison MediPharma (US), Inc.
Legal entity responsible for the study
Hutchison MediPharma, Limited.
Funding
Hutchison MediPharma, Limited.
Disclosure
N. Fowler: Honoraria (self), Research grant / Funding (self): Celgene; Honoraria (self), Research grant / Funding (self): Gilead Sciences; Honoraria (self), Research grant / Funding (self): Pharmacyclics; Honoraria (self), Research grant / Funding (self): Roche Pharma AG. W. Jurczak: Advisory / Consultancy, Research grant / Funding (self): Gilead Sciences; Advisory / Consultancy, Research grant / Funding (self): Janssen; Advisory / Consultancy, Research grant / Funding (self): Roche; Advisory / Consultancy, Research grant / Funding (self): Acerta; Advisory / Consultancy, Research grant / Funding (self): Celgene; Advisory / Consultancy: Celtrion; Advisory / Consultancy, Research grant / Funding (self): Sandoz-Novartis; Research grant / Funding (self): Beigene; Research grant / Funding (self): TG Therapeutics; Research grant / Funding (self): Incyte; Research grant / Funding (self): Bayer; Research grant / Funding (self): MediPharma; Research grant / Funding (self): AbbVie. R. Cordoba Mascunano: Advisory / Consultancy, Travel / Accommodation / Expenses: AbbVie; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Celgene; Advisory / Consultancy, Speaker Bureau / Expert testimony: Gilead; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Janssen; Advisory / Consultancy, Speaker Bureau / Expert testimony, Travel / Accommodation / Expenses: Roche; Advisory / Consultancy: Takeda; Advisory / Consultancy, Speaker Bureau / Expert testimony: Servier; Speaker Bureau / Expert testimony: Bristol-Myers Squibb. P. Abrisqueta Costa: Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Janssen; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: AbbVie. C. Yang: Shareholder / Stockholder / Stock options, Full / Part-time employment: Hutchison MediPharma Ltd. M. Kania: Shareholder / Stockholder / Stock options, Full / Part-time employment: Hutchison MediPharma Ltd. J. Kauh: Shareholder / Stockholder / Stock options, Full / Part-time employment: Hutchison MediPharma Ltd. A.J.M. Ferreri: Advisory / Consultancy, Speaker Bureau / Expert testimony: Kite Pharma; Advisory / Consultancy, Travel / Accommodation / Expenses: Gilead Sciences; Advisory / Consultancy, Research grant / Funding (self), Travel / Accommodation / Expenses: Celgene; Research grant / Funding (self), Travel / Accommodation / Expenses: Roche Pharma AG. All other authors have declared no conflicts of interest.
Resources from the same session
4925 - Prognostic role of CD73 in metastatic Non Small Cell Lung Cancer according to the presence of driver alterations
Presenter: Giulia Galli
Session: Poster Display session 1
Resources:
Abstract
785 - JAK-STAT inhibitor overcomes interferon γ-reduced, NK cell-mediated cytotoxicity in non-small-cell lung cancer cells
Presenter: Riki Okita
Session: Poster Display session 1
Resources:
Abstract
2326 - Low LATS2 expression is associated with poor prognosis in non small cell lung cancer
Presenter: Si-hyong Jang
Session: Poster Display session 1
Resources:
Abstract
5960 - Application of ESCAT and OncoKB scales in Liquid biopsy (LB) in Advanced NSCLC patients (pts): Is it feasible and reliable?
Presenter: Michael McCusker
Session: Poster Display session 1
Resources:
Abstract
4855 - IDH1R132H mutation induces a less aggressive phenotype of glioma cells and affects the radiosensitivity by interacting with Wnt/β-catenin signaling
Presenter: Xuetao Han
Session: Poster Display session 1
Resources:
Abstract
2641 - Impact of Angiopoietin-2 on glioblastoma response to combined chemo-radiotherapy
Presenter: Charly Helaine
Session: Poster Display session 1
Resources:
Abstract
5743 - The Discovery of RNA-aptamers That Selectively Bind and Inhibit Glioblastoma Stem Cells by targeting EphA2
Presenter: Alessandra Affinito
Session: Poster Display session 1
Resources:
Abstract
4160 - Impact of tumor reoxygenation by nanoparticles on Tumor Associated Macrophages (TAMs)
Presenter: Aurélie Ferré
Session: Poster Display session 1
Resources:
Abstract
2474 - Prognostic significance of c-Rel/p50 heterodimer in the tumor microenvironment of uveal melanoma
Presenter: Seema Kashyap
Session: Poster Display session 1
Resources:
Abstract
1769 - Synergistic role of BAP1 and DNA damage response pathway in uveal melanoma and its prognostic significance.
Presenter: JAYANTI JHA
Session: Poster Display session 1
Resources:
Abstract