HuMax-CD20, a Novel Fully Human Anti-CD20 Monoclonal Antibody: Results of a Phase I/II Trial in Relapsed or Refractory Follicular Non-Hodgkins’s Lymphoma.

The fully human monoclonal IgG₁ antibody HuMax-CD20 targets a novel epitope of the CD20 molecule on B-cells. HuMax-CD20 stops growth of engrafted B-cell tumors in SCID mice more efficiently and exerts stronger complement activation than Rituximab. HuMax-CD20 kills Rituximab-resistant cells expressing low levels of CD20. Data are presented from an ongoing, open label, dose-escalation, multicenter clinical trial in patients with relapsed or refractory CD20⁺ follicular non-Hodgkin’s lymphoma. Four cohorts of 10 patients were treated with 4 weekly i.v. infusions of 300, 500, 700 or 1000 mg. The endpoints are adverse events, CT verified tumor response (central review) according to the Cheson criteria, B-cell depletion, time to next anti-lymphoma treatment, duration of response, BCL2 conversion and pharmacokinetics. Fourty patients have been treated. Mean age was 57 years; median number of prior treatment regimens was 2; 15 patients were previously treated with Rituximab. Rapid, efficient and sustained peripheral B-cell depletion was observed in all dose groups. No dose limiting toxicity has been reported. Only 8 short lasting episodes of grade 3 CTC were observed. Hematological toxicity was low and confined to 6 events of grade 1 neutropenia; no cases of thrombocytopenia were reported. The following pharmacokinetic parameters were derived (medians per dose group): Cmax 129, 185, 380 and 610 μg/ml, T½ 447, 245, 322 and 621 hr, Cl 9, 19, 10 and 7 ml/hr/kg and AUC 75000, 51000, 185000 and 326000 hr *μg/ml, for the 300, 500, 700 and 1000 mg dose groups, respectively. No correlation between pharmacokinetics and response was found. Objective responses (CR, CRu, PR) have been elevated in 36 patients and were obtained in all 4 dose groups; 4 CR + 1 CRu/8 (300mg), 1CR + 2 PR/9 (500mg), 2PR/10 (700mg) and 1 CRu + 4 PR/9 (1000mg). Objective responses were achieved in 8 of 14 (57%) evaluable patients previously treated with Rituximab, i.e. 3CR, 1 CRu and 4 PR. In total 18 patients showed stable disease; progression was observed in only 3 patients. Data on duration of response will be presented. In conclusion, this preliminary analysis demonstrates a favorable safety profile and encouraging efficacy of HuMax-CD20 in patients with follicular NHL. Objective responses were achieved in all dose groups with response rates up to 63% including a 57% response rate in patients previously treated with Rituximab.