A phase I trial of TRU-016, an anti-CD37 small modular immunopharmaceutical (SMIP) in relapsed and refractory CLL

Abstract

3017 Background: CD37 is a tetraspan family member expressed predominantly on normal and transformed B-cells across a wide range of maturational stages. TRU-016 is a novel humanized anti-CD37 SMIP. Pre-clinical studies have demonstrated CD37 SMIP mediates significantly greater direct and NK-cell mediated killing of CLL cells as compared to other therapeutic antibodies used in CLL. A phase I study with TRU-016 was initiated based upon these data. Methods: Patients with relapsed/refractory CLL or SLL who had adequate organ function, platelets > 30,000/mm3 were eligible. Six doses and two different schedules (cohorts 1–8) have/or will be studied. The planned doses range from 0.03 mg/kg to 10 mg/kg IV once a week for 4 doses (cohort 1–6). The second schedule (cohort 7–8) will test 3.0 or 10.0 mg/kg on days 1, 3, and 5 the first week followed by 3 weekly doses. Dose escalation and de-escalation is based on CTC AE toxicity grades. Results: To date, 10 patients have been enrolled (cohort 1–5) and completed treatment; 1 patient (cohort 1–3: 0.03, 0.1, and 0.3 mg/kg); 3 patients at 1.0 mg/kg, and 4 patients at 3.0 mg/kg. Eight of the 10 have high risk genomic features [del(17p13.1), n=5 and del(11q22.3), n=3]. No dose limiting toxicities or serious adverse events have occurred. Mild (grade 1–2) infusion toxicity has been observed in 3 patients. Beginning with the 0.3 mg/kg dose, all eight patients demonstrated evidence of biological activity including patients with del(17p13.1). Two patients had partial clearing of leukemia cutis, and the other six had 27–94% reduction in peripheral lymphocyte count. One pt. had an increase in Hgb of 40% and a reduction in lymph nodes of 36%. Two patients had a significant increase in platelet count. Enrollment to cohort 6 is complete and further up-to-date data will be presented. Conclusions: To date, TRU-016 is a well tolerated treatment with minimal infusional toxicity and no observed dose limiting toxicity. Encouraging reduction in tumor lymphocyte blood counts, lymph node/spleen size and improvement in normal hematopoeitic function in patients with high risk genomic CLL have already been observed at low, non-saturating doses of CD37. Future single agent and combination studies of Tru16 in CLL are warranted. [Table: see text]