Promising Efficacy with the New Anti-CD20 Antibody GA101 In Heavily Pre-Treated NHL Patients – First Results From a Phase II Study In Patients with Relapsed/Refractory DLBCL and MCL

GA101 is the first type II, glycoengineered and humanized monoclonal anti-CD20 antibody with Phase I (Salles, ASH 2008, 2009; Cartron, EHA 2009; Morschhauser, ASH 2009; Sehn, ASH 2009) and indolent NHL phase II results (Salles, EHA, 2010) previously reported.

Forty eligible patients [25 DLBCL/15 MCL] were randomized to receive GA101 in a low-dose (LD, n=21 [10 DLBCL/11 MCL]) or a high dose (HD, n=19 [15 DLBCL/4 MCL]) 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 thereafter. 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 progression free survival (PFS).

Patients (Table 1) were heavily pre-treated (median 3 prior therapies), with 63% of patients not responding to or relapsing within six months after a previous rituximab-containing regimen (rituximab refractory) and 45% of patients completed all 9 infusions. For the LD cohort, EOR was 24% 5/21 (DLBCL – 2 PR, 1 CRu; MCL – 2 CR) and 32% (6/19) in the HD cohort (DLBCL – 4 PR; MCL – 2 PR). For DLBCL patients EOR was:28% (7/15) (1 CRu, 6 PR). For MCL patients EOR was: 27% (4/15) (2 CR, 2 PR). Of 13 refractory patients in LD, 1 patient achieved PR (8%) and of 12 refractory patients in HD, 3 patients achieved PR (25%), with two converting to CR during additional follow-up. Median PFS was 78 days [8-356+] and 83 days [7-428+] for the LD and HD cohorts respectively (Hazard ratio 0.88 [95% CI 0.43;1.79]).The most common AEs were G1-2 infusion related reactions (LD 81%, HD 68% of patients). Fourteen patients experienced at least one SAE during treatment period (LD=9, HD=5), with 7 related to GA101 (LD n=5, HD n=2), and 5 of these events associated with the first infusion (IRR=3; TLS=2), one after day 8 infusion (pyrexia), and one after cycle 6 infusion (bradycardia). During treatment, related G3-4 hematological AEs were transient neutropenia (n = 1 in HD), anemia (n = 2 in LD) and thrombocytopenia (n = 3 in LD). Ten patients had at least one G1-2 infection (5 in each cohort) with no G3-4 infections reported. GA101 plasma profiles were explored reflecting that mantle cell lymphoma patients in the HD (n=4) and LD (n=10) appeared to show lower plasma concentrations compared to DLBCL patients. There were 17 patient deaths reported (LD=11, HD=6), with 14 due to PD and 3 due to AE (1 during treatment period; cardio-respiratory arrest; not GA101-related) and two SAEs (LD) in follow-up (gastric haemorrhage, lung infection – both not GA101-related).

In this group of heavily pre-treated DLBCL and MCL patients, single-agent GA101 was well tolerated with promising evidence of efficacy.

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