Valemetostat for patients with relapsed or refractory peripheral T-cell lymphoma (VALENTINE-PTCL01): a multicentre,...

Area of Science:

• Oncology
• Hematology
• Pharmacology

Background:

• Peripheral T-cell lymphomas (PTCL) are aggressive non-Hodgkin lymphomas with limited treatment options for relapsed or refractory disease.
• Valemetostat tosylate is a novel dual inhibitor targeting EZH2 and EZH1 enzymes.
• Investigated the clinical activity and safety of valemetostat in PTCL and adult T-cell leukemia/lymphoma (ATLL).

Purpose of the Study:

• To evaluate the efficacy and safety of valemetostat in patients with relapsed or refractory PTCL.
• To assess the safety and tolerability of valemetostat in patients with relapsed or refractory ATLL.

Main Methods:

• A multicenter, open-label, single-arm, phase 2 trial (VALENTINE-PTCL01) enrolled patients aged 18+ with ECOG performance status 0-2.
• Patients received oral valemetostat 200 mg daily until disease progression or toxicity.
• Primary efficacy endpoint for PTCL was objective response rate (ORR) by BICR; primary safety endpoint for ATLL was safety and tolerability.

Main Results:

• 133 patients with relapsed/refractory PTCL and 22 with ATLL were enrolled.
• Objective response rate (ORR) in efficacy-evaluable PTCL patients was 44% (95% CI 35-53).
• Most common grade 3-4 adverse events included thrombocytopenia (23% PTCL, 50% ATLL), anemia (19% PTCL, 46% ATLL), and neutropenia (17% PTCL, 18% ATLL). Serious treatment-emergent adverse events occurred in 40% of PTCL patients and 68% of ATLL patients.

Conclusions:

• Valemetostat treatment resulted in durable responses for patients with relapsed or refractory PTCL.
• The safety profile of valemetostat was manageable in the studied patient populations.
• These findings support valemetostat as a potential therapeutic option for PTCL.