Voxtalisib shows promising efficacy in R/R FL but not for other iNHL and CLL

A phase II non-randomized, open-label trial (NCT01403636) assessed the safety and efficacy of voxtalisib (XL765/SAR245409) in patients with specific lymphoma subtypes or leukemia. Voxtalisib is a reversible inhibitor of phosphoinositide-3 kinase (PI3K) and a weak inhibitor of the mammalian target of rapamycin (mTOR). The study by Jennifer Brown, medical oncologist at the Dana-Farber Cancer Institute, Boston, was published by The Lancet Haematology online on 14 March 2018.

Study Overview

• Patients were enrolled from 30 oncology clinics in USA, Europe and Australia
• Total number of patients (N = 167) enrolled in the study were diagnosed with relapsed or refractory (R/R); mantle cell lymphoma (MCL) n = 42, follicular lymphoma (FL) n = 47, diffuse large B-cell lymphoma (DLBCL) n = 42 and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) n = 36
• Patients received 50 mg oral voxtalisib twice daily in 28-day continuous cycles until disease progression or unacceptable toxicity
• The primary endpoint of the study was overall response rate (ORR) for each of the disease subtypes. Secondary endpoints included progression-free survival (PFS), duration of response (DOR) and safety

Key Findings

• Median follow-up for all patients = 16.4 weeks
• ORR for each subtype:
  • MCL = 11.9% (95% CI, 4.0–25.6%)
    • Complete response (CR) = 7.1% and partial response (PR) = 4.8%
  • FL = 41.3% (95% CI, 27.0–56.8%)
    • CR = 10.9% and PR = 30.4%
  • DLBCL = 4.9% (95% CI, 0.6–16.5%)
    • CR = 0% and PR = 4.9%
  • CLL/SLL = 11.4% (95% CI, 3.2–26.7%)
    • CR = 0% and PR = 11.4%
  • Median PFS for each subtype:
    • MCL = 8.9 weeks (95% CI, 7.86–12.86)
    • FL = 58.0 weeks (95% CI, 26.00–not calculated)
    • DLBCL = 7.1 weeks (95% CI, 5.14–8.14)
  • CLL/SLL = 24.1 weeks (95% CI, 16.57–31.57

Safety

• Most common adverse events grade ≥3:
  • Anemia n = 21 (13%), pneumonia n = 15 (9%), fatigue n = 10 (6%) and diarrhea n = 5 (3%)
  • 53 patient deaths were reported (32%), 43 deaths were due to disease progression and 8 due to adverse events considered unrelated to the study

From the results, voxtalisib demonstrated some promising efficacy in FL but not in the other lymphoma subtypes or CLL. The authors noted that voxtalisib had an acceptable safety profile and that it might therefore warrant further its study for the FL subtype.