The results support further studies of CAL-101 at a dosage of 150 mg twice daily as a frontline therapy for CLL patients, or as a single agent or combined with chemoimmunotherapy for CLL patients, Dr. Furman added.
Calistoga Pharmaceuticals sponsored the trial. Dr. Furman had no financial conflicts to disclose. Several coauthors disclosed consultancy for, employment with, or research funding from Calistoga Pharmaceuticals; seven were employees and/or held equity ownership in the company.
TRU-016 Tackles CD37
Dr. Furman also presented results from a dose-escalation study of TRU-016, a novel humanized anti-CD37 small modular immunopharmaceutical (SMIP) protein.
Studies in mice have suggested that CD37 is involved in regulating B-cell function. TRU-016 offers direct apoptosis with greater cell-killing potential than rituximab and greater antibody-dependent cellular cytotoxicity than rituximab or alemtuzumab, he said.
In this dose-finding study, 57 patients with relapsed or refractory CLL or SLL received one of nine dosages, ranging from 0.03 mg/kg to 20 mg/kg, given intravenously once a week for 4-12 weekly doses. In a second dosing schedule, patients received 3, 6, or 10 mg/kg on days 1, 3, and 5 of the first week of treatment, followed by 3-11 weekly doses three times a week. The patients had no organ function problems, and their platelet counts were greater than 30,000/mcL.
The overall response rate was 13%, based on 1996 National Cancer Institute criteria. The overall median reduction in lymphocytes in the intent-to-treat population was 60%.
In the 16 patients with one to two prior therapies, the overall response rate was 40% and the clinical response rate was 44%. No clinical response was noted in patients with three or more prior therapies, but there was an overall median reduction in lymphocytes of 60% from baseline to the end of treatment, Dr. Furman said. The median progression-free survival for all patients was 134 days.
Neutropenia, the most common adverse event, was reported in nine patients (16%). There was no apparent relationship between drug dose and adverse events, and a maximum tolerated dose was not reached in this study.
"Given B-cell selective target, independent single agent activity, and synergy with CLL therapies, TRU-016 combination trials in CLL patients are planned," he said.
Trubion Pharmaceuticals (now Emergent Biosolutions) sponsored the trial. Dr. Furman had no financial conflicts to disclose. Several coinvestigators disclosed consultancy for, employment with equity ownership in, or research funding from Trubion.