Single-agent activity of GCS-100, a first-in-class galectin-3 antagonist, in elderly patients with relapsed chronic lymphocytic leukemia

7006 Background: GCS-100 is a polysaccharide antagonist of galectin-3, a protein whose overexpression on certain tumor cells is associated with poor prognosis in cancer patients. GCS-100 has been shown to induce apoptosis of patient CLL cells ex vivo. In addition, GCS-100 potentiates the in vitro activity of other agents commonly used to treat CLL, including rituximab. This phase II clinical trial evaluated the potential of GCS-100 as a novel single-agent therapeutic for relapsed CLL. Methods: Patients with Rai Stage II or higher CLL who had relapsed after one or two prior therapies were eligible. Prior therapies included a range of chemotherapy combinations including FCR, cyclophosphamide/vincristine/rituximab, and chlorambucil/prednisone. Patients received GCS-100 i.v. at 160 mg/m2 for 5 days every 21 days until disease progression. Peripheral blood was collected on study days 1, 4, and 8 of each cycle to assess peripheral leukocyte counts and apoptosis. CD38 and Zap70 expression were assessed where possible. Results: 24 pts were enrolled;16 men and 8 women (median age 67 years, range 40–86 years, 15/24 pts were over 65 years). GCS-100 was well-tolerated. There were no cases of drug-related grade 3 or 4 hematological toxicity or other serious AE. Two patients discontinued treatment due to rash, which resolved with cessation of treatment and which has been shown to be responsive to steroids. Six (25%) patients experienced PR, including 4 patients with >50% shrinkage of lymph node lesions. Currently 6 patients remain on study with a median duration of 5 months (range 4.5–9 months). In addition, apoptosis of peripheral leukocytes was confirmed by caspase activation and by DNA fragmentation. Conclusions: GCS-100 has significant single-agent activity in relapsed CLL. Its lack of myelosuppression and potential synergy with other agents makes GCS-100 a strong candidate for further development in CLL, particularly for elderly patients for whom there is a major need for less toxic agents. [Table: see text]