A Phase 2 Study of the Thrombospondin-Mimetic Peptide ABT-510 in Patients with Refractory Lymphoma.

ABT-510 is a potent nonapeptide that mimics the antiangiogenic activity of the endogenous protein, thrombospondin-1. Dogs with spontaneous lymphoma showed a response rate of 17% (4/23). In 2 phase 1 studies in patients with solid tumors, ABT-510 was tolerated at doses up to 260 mg per day. Doses ≥20 mg daily exceeded the pharmacokinetic target of 100 ng/mL for >3 hours. 67 patients with relapsed or refractory lymphoma were randomized to receive ABT-510 10 mg or 100 mg twice daily (BID) by subcutaneous injection. The 10 mg BID arm was discontinued after 15 patients were enrolled to consolidate recruitment to the higher dose. The primary endpoint was tumor response; secondary endpoints included progression-free survival (PFS) and overall survival. Tumor progression was evaluated every 8 weeks by the Cheson criteria; safety was evaluated every 4 weeks. 6 of the 67 patients remain on active therapy. Data are available for 56 patients (32M/24F); the median age is 63 years (range 22–87), and the baseline ECOG Performance Score for all patients ranges from 0–2. All patients were heavily pretreated, with a median of 5 prior treatments (range 1–11). There are 3 partial responses, all in the 100 mg dose group in non-Hodgkins lymphoma (NHL) patients. PFS data are as follows:

The most frequent adverse events (AEs) were asthenia (39%), injection site reaction (39%), diarrhea (24%), and anorexia (20%). 19% of patients had Grade 3–4 AEs considered related to ABT-510: anemia (4), thrombocytopenia (2), asthenia, chest pain, hemorrhage, gastrointestinal hemorrhage, leukopenia, and hypercalcemia (1 each). Correlative analyses of circulating endothelial cell data are pending. Based on these preliminary data, ABT-510 appears well-tolerated with biological activity in heavily pretreated patients with lymphoma. Study of ABT-510 in combination with immunotherapy or standard chemotherapy is warranted.