Abstract

Abstract 2878

Background:

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.

Methods:

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).

Results:

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).

Conclusion:

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

Table 1:

Baseline patient characteristics and response data

LD Cohort (400mg)HD Cohort (1600/800mg)All
n 21 19 40 
DLBCL histology (n) 10 15 25 
MCL histology (n) 11 15 
Median age (range) 70 (43–80) 72 (22–85) 71 (22–85) 
Median # of prior treatments (range) 4 (1–17) 3 (1–6) 3 (1–17) 
Previous rituximab (n) 21 19 40 
Rituximab refractory (n) 13 12 25 
Prior stem cell transplant (n) 
Response Data    
EOR 5 (24)% 6 (32%) 11 (28%) 
EOR (DLBCL only) 3 (30%) 4 (27%) 7 (29%) 
EOR (MCL only) 2 (18%) 2 (50%) 4 (27%) 
EOR Rituximab-refractory 1 (8%) 3 (25%) 4 (16%) 
Median PFS (days) 78 days [8–356] 83 days [7–428]  
Hazard ratio 0.88 [95% CI 0.43;1.79]   
Median PFS (DLBCL only) 57 days [8–351] 83 days [7–428]  
Hazard ratio 0.79 [95% CI 0.32; 1.92]   
LD Cohort (400mg)HD Cohort (1600/800mg)All
n 21 19 40 
DLBCL histology (n) 10 15 25 
MCL histology (n) 11 15 
Median age (range) 70 (43–80) 72 (22–85) 71 (22–85) 
Median # of prior treatments (range) 4 (1–17) 3 (1–6) 3 (1–17) 
Previous rituximab (n) 21 19 40 
Rituximab refractory (n) 13 12 25 
Prior stem cell transplant (n) 
Response Data    
EOR 5 (24)% 6 (32%) 11 (28%) 
EOR (DLBCL only) 3 (30%) 4 (27%) 7 (29%) 
EOR (MCL only) 2 (18%) 2 (50%) 4 (27%) 
EOR Rituximab-refractory 1 (8%) 3 (25%) 4 (16%) 
Median PFS (days) 78 days [8–356] 83 days [7–428]  
Hazard ratio 0.88 [95% CI 0.43;1.79]   
Median PFS (DLBCL only) 57 days [8–351] 83 days [7–428]  
Hazard ratio 0.79 [95% CI 0.32; 1.92]   
Disclosure:

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

Author notes

*

Asterisk with author names denotes non-ASH members.