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Clinical Trial
. 2017 Feb;176(3):412-420.
doi: 10.1111/bjh.14447. Epub 2016 Dec 16.

Ublituximab (TG-1101), a novel glycoengineered anti-CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/or refractory chronic lymphocytic leukaemia: results of a phase 2 trial

Jeff P Sharman  1   2 , Charles M Farber  3 , Daruka Mahadevan  4 , Marshall T Schreeder  5 , Heather D Brooks  2   6 , Kathryn S Kolibaba  2   7 , Suzanne Fanning  2   8 , Leonard Klein  2   9 , Daniel R Greenwald  2   10 , Peter Sportelli  11 , Hari P Miskin  11 , Michael S Weiss  11 , John M Burke  2   12
Affiliations
Clinical Trial

Ublituximab (TG-1101), a novel glycoengineered anti-CD20 antibody, in combination with ibrutinib is safe and highly active in patients with relapsed and/or refractory chronic lymphocytic leukaemia: results of a phase 2 trial

Jeff P Sharman et al. Br J Haematol. 2017 Feb.

Abstract

Ibrutinib is effective in patients with chronic lymphocytic leukaemia (CLL); however, treatment resistance remains a problem. Ublituximab is a novel, glycoengineered anti-CD20 monoclonal antibody with single-agent activity in relapsed CLL. We report the results of a phase 2 study evaluating combination therapy with ibrutinib and ublituximab in patients with relapsed or refractory CLL. Patients received ibrutinib 420 mg once daily. Ublituximab was administered on days 1, 8 and 15 of cycle 1 followed by day 1 of cycles 2-6. Response assessments were completed at cycles 3 and 6; patients then continued on ibrutinib monotherapy per standard of care. Forty-one of 45 enrolled patients were evaluable for efficacy. Safety was consistent with prior experience for each drug, with infusion reactions the most prevalent adverse event. Combination therapy resulted in an overall response rate (ORR) of 88% at 6 months. In the 20 patients with high-risk features (17p or 11q deletions or TP53 mutation) and evaluable for efficacy, the ORR was 95%, with three patients (15%) achieving negative minimal residual disease. Median time to response was 8 weeks. Ublituximab in combination with ibrutinib resulted in rapid and high response rates. The long-term clinical benefit of ublituximab will be defined by an ongoing phase 3 trial (NCT 02301156).

Keywords: 17-p deletion; chronic lymphocytic leukaemia; high-risk; ibrutinib; ublituximab.

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Figures

Figure 1
Figure 1
Study design and treatment schema. Patients received ibrutinib daily beginning on day 1 of cycle 1. Ublituximab infusions were given on days 1, 8, and 15 of cycle 1 and on day 1 of cycles 2 through 6. Patients were assessed for response after months 2 and 5. Each cycle is 28 days.
Figure 2
Figure 2
Best ORR. Forty‐one patients were evaluable for efficacy. Per iwCLL criteria (Hallek et al, 2008), the ORR within 6 months was 88% with 5% CR and 83% PR. When PR‐L is included, the ORR is 90%. In the high‐risk CLL population (n = 20), the ORR per iwCLL criteria was 95%, with 10% CR and 85% PR. CLL, chronic lymphocytic leukaemia; CR, complete response; iwCLL, International Workshop for Chronic Lymphocytic Leukaemia; ORR, overall response rate; PR, partial response; PR‐L, partial response with lymphocytosis.
Figure 3
Figure 3
Best per cent change from baseline in nodal size: efficacy assessed at weeks 8 and 20. Thirty‐eight of the 41 evaluable subjects, including all subjects with high‐risk CLL (n = 41), achieved a ≥50% reduction in nodal size from baseline. Three subjects with high‐risk CLL achieved MRD(−) status. CLL, chronic lymphocytic leukaemia; MRD(−), negative status for minimal residual disease.
Figure 4
Figure 4
ALC by month on treatment. ALC decreased by a median of 75% from baseline by the end of cycle 3. Within 6 cycles of therapy, 70% of subjects had an ALC in the normal range (<4 × 109/l). Vertical bars indicate the interquartile range. ALC, absolute lymphocyte count; CLL, chronic lymphocytic leukaemia.
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