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
1701 - Immunogenicity and optimal timing of 13-valent pneumococcal conjugate vaccination during adjuvant chemotherapy in gastric and colorectal cancer : A randomized controlled trial
Presenter: Wonyoung Choi
Session: Poster Display session 1
Resources:
Abstract
3158 - Tobacco Retail Access and Tobacco Cessation Among Head and Neck Cancer (HNC) Survivors
Presenter: Lawson Eng
Session: Poster Display session 1
Resources:
Abstract
5511 - ASSERT: A Prospective, Observational Study Measuring Sodium Improvement and Outcomes in Patients Treated for Moderate to Severe Hyponatremia Secondary to Syndrome of Inappropriate Antidiuretic Hormone secretion (SIADH) in Italy (Lung Cancer Cohort)
Presenter: Rossana Berardi
Session: Poster Display session 1
Resources:
Abstract
3821 - Efficacy and safety of controlled ovarian stimulation with or without letrozole co-administration for fertility preservation: A systematic review and meta-analysis.
Presenter: Benedetta Bonardi
Session: Poster Display session 1
Resources:
Abstract
2168 - Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy
Presenter: Tineke Vandenbroucke
Session: Poster Display session 1
Resources:
Abstract
5855 - Update of the registry of young women with cancer by the International Network of Cancer, Infertility and Pregnancy
Presenter: Charlotte Maggen
Session: Poster Display session 1
Resources:
Abstract
5156 - Erectile dysfunction in patients with metastatic renal cell carcinoma
Presenter: Ilya Tsimafeyeu
Session: Poster Display session 1
Resources:
Abstract
4992 - Exercise level, interest and preferences in cancer patients.
Presenter: Alice Avancini
Session: Poster Display session 1
Resources:
Abstract
3427 - Filling the Gaps in Informed Consent for Advanced Cancer Patients considering Phase 1 Oncology Trials - an in-depth Qualitative Study of Key Stakeholders at a large United Kingdom Phase 1 unit
Presenter: Abhijit Pal
Session: Poster Display session 1
Resources:
Abstract
3537 - Breast Cancer Patients’ Quality of Life: Real World Data
Presenter: Thanos Kosmidis
Session: Poster Display session 1
Resources:
Abstract