Rocbrutinib, a Highly Selective Fourth-Generation Covalent and Noncovalent BTK Inhibitor, in R/R Non-GCB DLBCL:...

Area of Science:

• Oncology
• Pharmacology
• Hematology

Background:

• Rocbrutinib is a novel fourth-generation Bruton's tyrosine kinase (BTK) inhibitor.
• It targets both wild-type and mutant BTK variants, including C481.
• This study focuses on its application in Chinese patients with relapsed or refractory (R/R) non-germinal center B cell-like (non-GCB) diffuse large B cell lymphoma (DLBCL).

Purpose of the Study:

• To evaluate the pharmacokinetics (PK), safety, and efficacy of rocbrutinib.
• To determine the optimal dose for further clinical trials.
• To assess rocbrutinib's potential in a heavily pre-treated patient population.

Main Methods:

• A Phase I clinical trial involving adult patients with R/R non-GCB DLBCL who received at least two prior therapies.
• Patients were administered rocbrutinib daily at doses of 100, 150, 200, or 300 mg.
• Efficacy was assessed using CT and PET-CT scans, with PK and adverse events meticulously monitored.

Main Results:

• An overall response rate (ORR) of 57.8% and a complete response (CR) rate of 33.3% were observed in 45 enrolled patients.
• In the cohort receiving ≥200 mg QD (n=18), the ORR was 72.2% and CR rate was 44.4%.
• Treatment-emergent adverse events (TEAEs) occurred in 97.8% of patients; however, only 2.2% discontinued treatment due to TEAEs. Notably, no atrial fibrillation/flutter was reported.

Conclusions:

• Rocbrutinib demonstrates significant efficacy and a well-tolerated safety profile in Chinese patients with R/R non-GCB DLBCL.
• A 200 mg QD dose was identified as the recommended Phase 2 dose for monotherapy.
• A Phase II clinical trial is currently underway to further investigate rocbrutinib in this patient group.