New Clinical Trial: Phase 1 Dose-escalation Study Evaluating the Safety, Pharmacodynamics, Pharmacokinetics, & Efficacy of GS-9901 in Subjects with Relapsed or Refractory Follicular Lymphoma, Marginal Zone Lymphoma, CLL/SLL

The Weill Cornell Lymphoma Program has recently opened a new clinical trial for men and women with follicular lymphoma, marginal zone lymphoma, and CLL/SLL. The study sponsor is Gilead Sciences Inc., and the principal investigator at Weill Cornell is Richard Furman M.D.. For more information about the study, please call Amelyn Rodgriguez, RN at (212) 746-1362 or e-mail Amelyn at amr2017@med.cornell.edu.

Key Eligibility

  • Men and women age 18 and older.
  • Diagnosis of FL, MZL, or CLL/SLL.
  • Prior treatment with at least 1 chemotherapy or immunotherapy-based regimen.
  • Detailed eligibility reviewed when you contact the study team.

Study Details 

This clinical trial is for men and women with relapsed/refractory FL, MZL, or CLL/SLL.

GS-9901 is a second generation inhibitor of PI3K-delta which is critical for multiple signaling pathways that are hyperactive in B-cell malignancies and inflammation. The first generation PI3K-delta inhibitor idelalisib has been shown to induce durable disease control in patients with B-cell malignancies. Idelalisib as monotherapy or in combination with other agents (such as bendamustine, chlorambucil) and immunotherapy (rituximab, ofatumumab) has been shown to be tolerable and demonstrated clinical efficacy in clinical trials in patients with iNHL, CLL, and other hematological malignancies. This study will provide more information about whether GS-9901 can benefit subjects with B-cell malignancies in terms of efficacy and tolerability compared to first generation PI3K inhibitors.

Subjects will receive GS-9901 continuously throughout the study as long as they are responding to therapy and not experiencing unacceptable side effects. GS-9901 is administered orally once daily. After discontinuing treatment, follow-up information will be collected once every year for up to 5 years at clinic visits or through telephone calls.

Updated Efficacy Results of Ibrutinib Compared with Ofatumumab in Relapsed CLL (RESONATE Trial), with Analysis of Genetic and Prognostic Subgroups

Picture3By Dr. Richard Furman, MD

The role of various prognostic factors in CLL/SLL is not yet fully understood, including the implications of new genetic markers associated with high risk. Ibrutinib is a first-in-class Bruton’s tyrosine kinase inhibitor that is approved for the treatment of CLL patients who have received at least 1 prior therapy, and for patients with 17p deletion CLL. In results presented before the 56th annual meeting of the American Society of Hematology, updated efficacy results from the phase 3 RESONATE (PCYC-1112) study comparing ibrutinib to ofatumumab were reported.

In the phase III study 391 randomized patients received 420 mg daily of ibrutinib or ofatumumab daily, until disease progression or unacceptable toxicity for up to 24 weeks. During an interim analysis at the median follow up of 9.4 months, patients in the ofatumumab arm were provided access to the ibrutinib arm.

Comparatively, progression free survival (PFS) was significantly longer for ibrutinib compared to ofatumumab. Overall survival (OS) was significantly better for ibrutinib compared to ofatumumab, with 18-month OS rates of 85% and 78% respectively. Higher number of prior therapies (≥3) and 11q deletion were associated with significantly lower 12-month PFS rate for ofatumumab, but not for ibrutinib. The overall response rate (ORR) for ibrutinib versus ofatumumab was 90% to 25%. Compared to ofatumumab, ibrutinib improved 12-month PFS and ORR regardless of baseline genetics, complex cytogenetics, or number of prior therapies. No significant difference in 12-month PFS was observed in ibrutinib treated patients with or without del(17p) or for those who developed lymphocytosis compared to those without lymphocytosis. Median treatment duration was longer for ibrutinib versus ofatumumab and was 16 to 5 months respectively.

In this one on one comparison ibrutinib significantly outperformed ofatumumab in PFS, OS, and ORR in patients with CLL/SLL with at least one prior therapy. These results are consistent with previously published findings, and provide further evidence for the clinical utility  of ibrutinib in patients with CLL.