Abstract 5239: A phase I study of HMPL-523, a small molecule, selective inhibitor of spleen tyrosine kinase, inpatients with relapsed or refractory lymphoma
Authors: Lawrence Tunde , Khullar Alisha , Yang Weiss , Hahka-Kemppinen Marjo , Kania Marek , Su Weigou 
Published: September 2020

Background:

B-cell receptor (BCR) signaling pathway plays crucial roles in the pathobiology of non-Hodgkin's lymphomas (NHL). Despite available agents targeting the BCR pathway, no agents are yet curative, remissions are usually not durable, and toxicities are often serious. Hence, there continues to be unmet medical needs for more effective and less toxic therapies in patients with relapsed/refractory (R/R) lymphoma.

HMPL-523 is a small molecule, orally available, highly selective inhibitor of spleen tyrosine kinase (SYK), a key kinase, and therapeutic molecular target in the BCR signaling pathway. There are currently ongoing global clinical studies with HMPL-523, in Australia, China, the EU (Italy, Spain & Poland), and the United States (US). Preliminary results from dose escalation and expansion stage for HMPL-523 are expected soon. Herein is the description of ongoing phase I open-labelled dose-escalation study including dose expansion stage.

Methods:

Study Population: The target population is adult patients with histologically confirmed relapsed or refractory HL or NHL. To be eligible for enrollment, patients must have exhausted all approved therapy options available.

Objectives: The primary objective is to assess the safety and tolerability of HMPL-523 in patients with relapsed or refractory lymphoma, and to determine the maximum-tolerated dose (MTD)/ recommended phase II dose (RP2D). Preliminary efficacy in patients with relapsed or refractory lymphoma will be evaluated as a secondary objective.

Study Design: Open-labelled, dose-escalation in R/R NHL pts, following a traditional 3+3 design. Anticipate up to 30 pts will enroll until MTD/RP2D is reached. The proposed doses are 100, 200, 400, 600 and 800 mg, oral, daily in a 28-day cycle. until disease progression, intolerable toxicity, no further benefit from treatment, withdrawal, end of study, or death.

Expansion stage will further evaluate clinical benefit of the study drug at MTD/RP2D in ~60 patients, with ~10 patients in each cohort of:

• Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL),

• Mantle cell lymphoma (MCL),

• Follicular lymphoma (FL)

• Marginal zone lymphoma (MZL)

• Peripheral T-Cell lymphoma (PTCL)

• Waldenström's macroglobulinemia/ lymphoplasmacytic lymphoma (WM)

Conclusions: Ongoing global studies are still open and enrolling patients with R/R lymphoma. Validated data / results from this study will be made available at the end of dose escalation and or at the conclusion of dose expansion stage.

Citation Format: Tunde Lawrence, Alisha Khullar, Weiss Yang, Marjo Hahka-Kemppinen, Marek Kania, Weigou Su. A phase I study of HMPL-523, a small molecule, selective inhibitor of spleen tyrosine kinase, inpatients with relapsed or refractory lymphoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5239.