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
2023 - Patients with brain metastases treated with afatinib in clinical practice – results from the prospective non-interventional study GIDEON
Presenter: Eckart Laack
Session: Poster Display session 1
Resources:
Abstract
1613 - Lerociclib (G1T38), an oral CDK4/6 inhibitor, dosed continuously in combination with osimertinib for EGFRmut non-small cell lung cancer: initial Phase 1b results
Presenter: David Berz
Session: Poster Display session 1
Resources:
Abstract
2853 - Real-world implementation of sequential targeted therapies for EGFR-mutated NSCLC
Presenter: Petros Christopoulos
Session: Poster Display session 1
Resources:
Abstract
1974 - A Phase II Open-Label, Multicentre Study to Assess the Anti-tumour Activity of Afatinib in Patients with Activating Epidermal Growth Factor Receptor mutation (EGFRm) from Circulating Tumor DNA (CtDNA)
Presenter: Young-Chul Kim
Session: Poster Display session 1
Resources:
Abstract
3370 - Influence of cow’s milk on the absorption and exposure of erlotinib in NSCLC patients
Presenter: Geerten Veerman
Session: Poster Display session 1
Resources:
Abstract
5900 - PTEN loss as Predictor of Tumor Heterogeneity (TH) and Poor Prognosis in EGFR-mutant Advanced Non-Small Cell Lung Cancer (ANSCLC) Patients (pts) Receiving Tyrosine-Kinase Inhibitors (TKIs).
Presenter: Miriam Ferrara
Session: Poster Display session 1
Resources:
Abstract
1302 - Safety of lorlatinib in subgroups of patients from a phase 1/2 trial
Presenter: Enriqueta Felip
Session: Poster Display session 1
Resources:
Abstract
1497 - Brigatinib (BRG) in Asian vs non-Asian patients (pts) with crizotinib (CRZ)-refractory ALK+ NSCLC in the phase 2 ALTA trial
Presenter: Dae Ho Lee
Session: Poster Display session 1
Resources:
Abstract
2349 - The safety assessment of crizotinib and alectinib from real world data of 840 ALK-inhibitor naïve patients with NSCLC harboring ALK-rearrangement (WJOG9516L).
Presenter: Kei Kunimasa
Session: Poster Display session 1
Resources:
Abstract
1120 - Brigatinib in ALK TKI-pretreated ALK+ metastatic non-small cell lung cancer (mNSCLC): the Use Via Expanded Access to Brigatinib (UVEA-Brig) study
Presenter: Silvia Novello
Session: Poster Display session 1
Resources:
Abstract