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Obinutuzumab (GA101) 1,000 mg versus 2,000 mg in patients with chronic lymphocytic leukemia (CLL): Results of the phase II GAGE (GAO4768g) trial.
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Background: Early phase 1/2 trials with GA101 in CLL demonstrated single-agent activity with suggestion of a dose response. GAGE (NCT01414205) is a multicenter, randomized study that evaluated GA101 at 2 doses in patients (pts) with symptomatic, untreated CLL. Methods: Randomization of 80 pts with intact organ function and ECOG PS <3 were stratified based on Rai stage (1–2 vs 3–4) and tumor mass (single lesion by CT scan, <5 cm vs ≥5 cm): GA101 1,000 mg (100 mg IV d1, 900 mg d2, 1000 mg d8, d15 of cycle 1; 1000 mg d1 of cycles 2–8) or 2000 mg (100 mg IV d1, 900 mg d2, 1,000 mg d3, 2,000 mg d8, d15 of cycle 1; 2,000 mg d1 of cycles 2–8). Each cycle was 21 days. ORR was assessed at 2 months post-therapy according to the International Workshop on CLL (iwCLL) criteria. Pts had similar pre-treatment demographics in the 2 arms. Median age was 67 (34–91) years, 36% women, 41% Rai stage 3-4, 29% with tumor masses ≥5 cm, 54% unmutated IGHV, and 10% del(17p13). Median follow-up was 11 months. Results: Key efficacy and safety results are shown in table below. Most frequent adverse event (AE) was infusion-related reactions (IRRs). No Grade (Gr) 3/4 IRRs occurred after cycle 1. A death (myocardial infarction) occurred after cycle 5, judged by site investigator as unrelated to GA101. Conclusions: These results demonstrated single-agent efficacy of GA101 at 1,000- and 2,000-mg doses, with a difference in ORR between the 2 arms (P = .08). No new safety signals were observed. Incidences of Gr 3/4 AEs were similar in each arm, except for IRRs. Further study is warranted to determine durability of response and long-term side effects of GA101. Clinical trial information: NCT01414205.
|Total N = 80||1,000 mg (n = 41)||2,000 mg (n = 39)|
|ORRa, n (%)||20 (49)||26 (67)|
|CR/CRi, n (%)||2 (5)||8 (21)|
|SD, n (%)||11 (27)||9 (23)|
|PD, n (%)||3 (7)||0 (0)|
|Unable to evaluate/missingc, n (%)||7 (17)||4 (10)|
|Gr 3-4 AE, %
aORR based on investigator-reported end-of-treatment response, which includes CT scan performed 51+ days from last GA101 dose bPvalue is 2-sided, based on stratified Cochran-Mantel-Haenszel test on ORR cPts classified as missing if no post-baseline response assessments were available or all post-baseline response assessment were performed <51 days from last GA101 dose.
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