1106TiP - A phase I study of HMPL-523, a selective oral anti-spleen tyrosine kinase inhibitor, in patients with relapsed or refractory lymphoma

Abstract

BackgroundThe 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 designStudy 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 (1pt only), 200, 400, 600, and 800mg, 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, andWaldenström’s macroglobulinemia/ lymphoplasmacytic lymphoma Clinical trial identificationNCT03779113. Editorial acknowledgementHoang-Lan Nguyen, Hutchison MediPharma (US), Inc. Legal entity responsible for the studyHutchison MediPharma, Limited. FundingHutchison MediPharma, Limited. DisclosureN. 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.