Promising Efficacy with the New Anti-CD20 Antibody GA101 In Heavily Pre-Treated NHL Patients – Updated Results with Encouraging Progression Free Survival (PFS) Data From a Phase II Study In Patients with Relapsed/Refractory Indolent NHL (iNHL)

GA101 is the first type II, glycoengineered and humanized monoclonal anti-CD20 antibody with Phase I results (NHL/CLL) (Salles, ASH 2008, 2009; Cartron, EHA 2009; Morschhauser, ASH 2009; Sehn, ASH 2009) and phase II results (Indolent NHL) previously reported (EHA 2010). Based on an additional 1 year follow-up period, we report updated efficacy and safety results with single agent GA101, presenting new and encouraging progression free survival (PFS) data indicating a survival advantage of those patients randomized to the high dose cohort (1600/800mg).

40 eligible patients were randomized to receive GA101 in a low-dose (LD, n=18) or a high dose (HD, n=22) cohort. GA101 was given on d1, d8, d22 and q21 days for total of 9 infusions. In the LD cohort, GA101 was given 400mg all infusions; in the HD cohort, d1 and d8 at 1600mg and 800mg for subsequent infusions. Primary endpoint was end of treatment response (EOR), assessed 4 weeks after last infusion (44 weeks after treatment start). Secondary objectives were safety, pharmacokinetics and PFS.

Patients (Table 1) were heavily pre-treated (median 3 prior therapies) with 55% of patients not responding to or relapsing within six months after a previous rituximab-containing regimen (rituximab refractory). There were no significant differences in demographics and baseline tumour burden between the two cohorts and 75% of patients completed all scheduled 9 infusions. EOR was 17% (3 PR, 6 SD, 7 PD, 2 UNK) in the LD cohort, and 55% (2 CR, 10 PR, 6 SD, 4 PD) in the HD cohort. Of note, 6/22 rituximab-refractory patients (5 HD, 1 LD) responded, with a EOR response of 50% in rituximab-refractory patients in the HD cohort (5/10). Responses occurred across all FcγIIIR genotypes in both cohorts: of 3 responders in LD, 2 patients with F/F genotype, other unknown; of 12 responders in HD; 5 F/F, 7 F/V. Responding patients from both LD and HD groups appeared to have higher GA101 plasma concentrations compared to non-responding patients. Median PFS was 6 months [1.1-16.9+ months] and 11.3 months [1.8-14.2+ months] for the LD and HD cohorts respectively (Hazard ratio 0.55 [95% CI 0.24;1.27]). Of 15 responding patients at EOR, 9 have an ongoing response in follow-up (LD=2, HD=7), with 2 PRs converting to CR (LD=1, HD=1) and another PR to CRu (HD). In addition 2 patients (LD=1, HD=1) in follow-up converted from EOR SD to PR, one patient with an ongoing response and the other subsequently relapsing, therefore 10 patients currently have an ongoing response. GA101 was well tolerated in both cohorts with the most common AEs being infusion related reactions (LD 72%, HD 73% of patients), mostly of G1-2. During treatment, related G3-4 hematological AEs were transient neutropenia (n = 3 in HD), febrile neutropenia (n=1 in HD) and thrombocytopenia (n = 1 in HD), four patients experienced at least one G3-4 Infection (LD n=1, HD n=3). Nine patients experienced a total 12 SAEs during treatment period, with 4 related to GA101 (HD n=4; herpes zoster, febrile neutropenia, pancreatitis, neutropenia) and 2 patients in the additional follow-up period, with SAEs of pyrexia (LD) and bacteraemia (HD), both unrelated to GA101. In addition, no B-cell recovery has been observed to date.

GA101 single agent is well tolerated, with promising efficacy and provides very encouraging PFS data, in this group of heavily pre-treated relapsed and refractory iNHL patients, indicating a survival advantage for those patients in the HD cohort (1600/800mg).

Salles:Roche: Consultancy, Honoraria. Morschhauser:Roche: Consultancy, Honoraria. Wenger:Roche: Employment. Birkett:Roche: Employment. Cartron:Roche: Consultancy, Honoraria; GSK: Honoraria.