Phase I study of novel SYK inhibitor TAK-659 (mivavotinib) in combination with R-CHOP for front-line treatment of high-risk diffuse large B-cell lymphoma.
EJHaem
; 4(1): 108-114, 2023 Feb.
Article
in En
| MEDLINE
| ID: mdl-36819145
ABSTRACT
Background:
TAK-659, a novel oral SYK inhibitor, has demonstrated efficacy in heavily pretreated diffuse large B-cell lymphoma (DLBCL). We report results of a phase I single-institution escalation study of front-line treatment with R-CHOP and TAK-659 in treatment-naïve high-risk DLBCL.Methods:
Patients with high-risk DLBCL were treated with R-CHOP for 1 cycle, followed by combined R-CHOP and TAK-659 for an additional five cycles, with TAK-659 dosing escalated from 60 mg, to 80 mg, to 100 mg daily, based on a 3 + 3 design. The primary objective was to determine the safety and establish the maximum tolerated dose (MTD) of TAK-659 in this setting.Results:
Twelve patients were enrolled. Dose level 3 (100 mg) was established as the MTD. Dose level 1 (60 mg) maintained a similar area under the curve (AUC) to the MTD. With a median follow-up of 21 months, 92% of patients achieved complete response (CR). The most common treatment-emergent adverse events were lymphopenia (100%), infection (50%, n = 3 opportunistic), aspartate aminotransferase elevation (100%), and alanine aminotransferase elevation (83%).Conclusion:
A TAK-659 dose of 60 mg was well tolerated, did not require dose modifications, and maintained a similar AUC to the MTD. The combination of R-CHOP and TAK-659 in patients with newly diagnosed high-risk DLBCL produces promising CR rates.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Type of study:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Language:
En
Journal:
EJHaem
Year:
2023
Document type:
Article