Phase I/II results of a second-generation humanized anti-CD20 antibody, IMMU-106 (hA20), in NHL

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Abstract
7530 Background: The humanized anti-CD20 antibody, IMMU-106 (hA20), has similar murine CDRs to rituximab, but the remaining framework is identical to humanized anti-CD22 IgG1 antibody, epratuzumab, whose safety and short infusion times have been reported. Methods: An open-label, multicenter, phase I/II, dose escalation study was conducted in adult patients with recurrent NHL to establish the safety, tolerance, PK, and immunogenicity (HAHA) of hA20 administered weekly x 4. Thirty-four patients have now received hA20 at 120 (n = 7), 200 (n = 6), 375 (n = 18) or 750 mg/m2 (n = 3). These were predominantly stage III/IV patients (n = 27) with follicular lymphoma (N = 23) who received 1–7 prior treatments (median, 2), including 1 (N = 22) or more (N = 9) rituximab regimens (without progression within 6 months). Results: Thirty-three patients completed all 4 hA20 infusions. Median infusion times at 375 mg/m2 were 3.1 h for 1st infusion, 2.0–2.3 h for subsequent infusions, and were generally shorter at lower doses. Fourteen patients (14%) had transient events, predominantly grade 1–2 events at 1st infusion. Antibody levels increased with hA20 dose; at 375 mg/m2, mean serum half-lives after 1st and 4th infusions were 3.4 ± 1.7 and 12.3 ± 3.9 days, respectively. With median follow-up now 3–6 months, peripheral blood B-cell depletion persists, HAHA evaluations are negative, and 14/23 patients (61%) with response assessments have objective responses by Cheson criteria. All 6 CR/CRu’s (23%) were in follicular lymphoma, occurred at all dose levels even at 120 mg/m2 (including patients with 2–4 prior rituximab-containing regimens ), and with 5/6 continuing. Conclusions: The tolerability, relatively short infusion times, and CR/CRu’s in patients with follicular lymphoma who relapsed after rituximab-containing regimens is encouraging. This study is continuing to assess response durability and to determine the optimal hA20 dose for subsequent studies. [Table: see text]

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