Phase I study of recombinant human CD40 ligand in cancer patients

Purpose: To determine the toxicity, maximum-tolerated dose (MTD), and pharm acokinetics of recombinant human CD40 ligand (rhuCD40L) (Avrend; Immunex Co rp, Seattle, WA), suggested in preclinical studies to mediate cytotoxicity against CD40-expressing tumors and immune stimulation. Patients and Methods: Patients with advanced solid tumors or intermediate- or high-grade non-Hodgkin's lymphoma (NHL) received rhuCD40L subcutaneously daily for 5 days in a phase I dose-escalation study. Subsequent courses we re given until disease progression. Results: Thirty-two patients received rhuCD40L at three dose levels. A tota l of 65 courses were administered. The MTD was 0.1 mg/kg/d based on dose-re lated but transient elevations of serum liver transaminases. Grade 3 or 4 t ransaminase elevations occurred in 14%, 28%, and 57% of patients treated at 0.05, 0.10, and 0.15 mg/kg/d, respectively. Other toxicities were mild to moderate. At the MTD, the half-life of rhuCD40L was calculated at 24.8 +/- 22.8 hours. Two patients (6%) had a partial response on study (one patient with laryngeal carcinoma and one with NHL), For the patient with laryngeal cancer, a partial response was sustained for 12 months before the patient w ets taken off therapy and observed on no additional therapy. Three months l ater, the patient was found to have a complete response and remains biospy- proven free of disease at 24 months. Twelve patients (38%) had stable disea se after one course, which wets sustained in four patients through four cou rses. Conclusion.: The MTD of rhuCD40L when administered subcutaneously daily for 5 days was defined by transient serum elevations in hepatic transaminases, Encouraging antitumor activity, including a long-term complete remission, was observed. phase II studies are warranted. (C) 2001 by American Society of Clinical Oncology.