Phase II study finds entospletinib has limited activity in patients with R/R DLBCL

A study by John Burke, Rocky Mountain Cancer Centers, the US oncology network, Aurora, Colorado, and colleagues was published in Clinical Lymphoma, Myeloma & Leukemia on the findings from the phase II open-label study of entospletinib monotherapy (GS-9973) in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).

Entospletinib is an oral, selective spleen tyrosine kinase inhibitor. A previous study assessed the safety, tolerability and efficacy of entospletinib with R/R hematologic malignancies (NCT01799889) however, only the results from chronic lymphocytic leukemia (CLL) cohort have been reported thus far.

Study Overview

• N = 43 patients with R/R DLBCL were included in the study and treated with a pre-determined recommended dose of 800 mg entospletinib twice daily
  • 65% of patients were male and the median age was 68 (range, 27–89)
  • The median number of prior lines of therapy was 2 (range, 1–7)
  • 42% of patients had germinal center B-cell (GCB) subtype and 39% had non-GCB subtype
• The primary endpoint of the study was progression-free survival at 16 weeks assessed by an independent review committee (IRC)
• The secondary endpoints included; safety, objective response rate (ORR), duration of response (DOR) and time-to-response assessed by an IRC

Key Findings

• The 16-week PFS rate was 3.6% (95% CI, 0.3–15.3%)
• The median PFS was 1.5 months (95% CI, 1.1–1.7 months)
• The most frequent adverse events (AEs) Grade ≥3 included: lymphocytopenia (37%), hyponatremia (12%), increased ALT (12%), fatigue (9%) and diarrhea (9%)
• 10 patients died of disease progression (n = 7) and 3 died of causes considered unrelated to study drug (septic shock, acidosis, and respiratory failure)

The authors concluded that the safety findings for the DLBCL cohort were similar to the other cohorts in the study. As monotherapy, entospletinib demonstrated limited activity in patients with R/R DLBCL. The authors suggested that there may be a need for clinical trials where entospletinib is used in combination therapy.