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
5344 - Global trends in population-based survival for 303,169 adults diagnosed with glioblastoma in 44 countries during 2000-2014 (CONCORD-3)
Presenter: Fabio Girardi
Session: Poster Display session 1
Resources:
Abstract
3088 - Spanish Survey of treatment recommendations for elderley patients with glioblastoma
Presenter: María Ángeles Vaz Salgado
Session: Poster Display session 1
Resources:
Abstract
3484 - Updated analysis of the National Registry of Nervous System Tumors in Spain (RETSINE). RETSINE: National Registry of Nervous System Tumors of the Spanish Research Group in Neuro-oncology (GEINO) and Spanish Infrequent and Orphan Tumors Group (GETHI)
Presenter: Isaac Ceballos Lenza
Session: Poster Display session 1
Resources:
Abstract
4737 - Development and validation of novel nomograms predicting survival of malignant ependymoma patients: A population-based study
Presenter: Alzhraa Abbas
Session: Poster Display session 1
Resources:
Abstract
4740 - Characteristics, incidence, and survival of primary cerebral lymphoma: A population based study
Presenter: Sherief Ghozy
Session: Poster Display session 1
Resources:
Abstract
5362 - Trends in Incidence and Survival Analyses of Adult-onset Medulloblastoma
Presenter: Feifei Lin
Session: Poster Display session 1
Resources:
Abstract
3868 - Meta of classical chemotherapy compared with high-dose chemotherapy combined with autologous stem cell transplantation in newly diagnosed medulloblastoma patients after radiotherapy
Presenter: Mengting Zhang
Session: Poster Display session 1
Resources:
Abstract
4446 - Effect of cumulative dose of maintenance temozolomide on overall survival in patients with high grade glia tumors: a single institution analysis
Presenter: Marta Nerone
Session: Poster Display session 1
Resources:
Abstract
5119 - Markers of systemic inflammation correlate with survival prognosis in patients with newly diagnosed brain metastases
Presenter: Angelika Starzer
Session: Poster Display session 1
Resources:
Abstract
3882 - Venous Thromboembolism and Intracranial Hemorrhage in Patients with High-grade Glioma
Presenter: Clara Borges
Session: Poster Display session 1
Resources:
Abstract