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Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients

Gilles Salles, Franck Morschhauser, Thierry Lamy, Noel Milpied, Catherine Thieblemont, Hervé Tilly, Gabi Bieska, Elina Asikanius, David Carlile, Joe Birkett, Pavel Pisa and Guillaume Cartron

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Figures

Tables

  • Table 1

    Patient demographics

    CharacteristicN = 21
    Sex, male/female9/12
    Median age, y (range)64 (39-83)
    Median time from diagnosis, y (range)5.9 (2.5-24.2)
    Median prior therapies, n (range)5 (1-8)
        Prior rituximab, n (%)20 (95)
        Rituximab-refractory, n (%)9 (43)
        Prior ASCT, n (%)6 (29)
        Prior fludarabine, n (%)5 (24)
    Median duration of response to last treatment, mo (range)16 (3-112)
    Baseline hematologic parameters, median (range)
        Hemoglobin, g/L123 (75-151)
        Neutrophils, 109/L3.27 (1.59-8.28)
        Platelets, 109/L172 (73-325)
    • ASCT indicates autologous stem cell transplantation.

    • * Refractory is defined as progression on treatment, stable disease, or partial response or better with progression < 6 months after any prior rituximab-containing therapy.

  • Table 2

    All Grade 3 or 4 AEs and additional AEs (all grades) occurring in more than 1 patient

    AEAll gradesGrade 3 or 4
    n%No. of eventsn%No. of events
    Any AE2110013273318
        Infusion-related reactions1886482103
        Cycle 1, day 1 (n = 21)178115
        Cycle 1, day 8 (n = 20)84015
        Cycle 2 (n = 19)526
        Cycle 3 or later (n = 16)638
    Infections*115216
    Asthenia838102102
    Diarrhea5247
    Thrombocytopenia4194151
    Anorexia4194151
    Weight loss4194
    Lymphopenia31433143
    Fatigue3143
    Nausea3143
    Insomnia3143
    Neutropenia21022102
    Anemia2102151
    Sciatica151151
    Extrinsic vascular compression151151
    Tumor lysis syndrome152152
    Leukopenia151151
    Axillary pain151151
    Cerebrovascular accident151
    • * The most common infection reported was bronchitis (n = 4). Herpesvirus infection occurred in 2 patients. All reported infections were grade 1 or 2.

    • The incidence of cerebrovascular accident was grade 5 and resulted in death. This 83-year-old patient had a low IgM level before treatment (115 mg/dL). IgM levels increased to 404 mg/dL after cycle 1, but returned to 107 mg/dL after cycle 2, 34 days before the cerebrovascular accident. Although no disease evaluation or IgM measurement was available before death, given this kinetic and the patient's underlying illness, the investigator judged that this event was unrelated to the study drug.

  • Table 3

    Symptoms of infusion-related reactions and other drug-related AEs, listed by frequency, experienced by 3 or more patients during infusion and within 24 hours after completion of infusion (N = 21)

    AEn%
    Patients with at least 1 AE1886
    Hypotension*1152
    Pyrexia1048
    Nausea*943
    Vomiting*838
    Chills*629
    Asthenia629
    Flushing314
    Headache314
    Larynx irritation314
    • * One patient experienced grade 3 hypotension, nausea, vomiting, and dizziness that resulted in the dosage being modified. Other grade 3 events were observed in a mantle cell lymphoma patient who experienced tumor lysis syndrome; events included asthenia, chills, dyspnea, headache, hyperkalemia, hyperthermia, leukopenia, and thrombocytopenia. No grade 4 infusion-related events were observed.

  • Table 4

    Response by dose group (best overall response)

    GA101 dose (mg)
    50/100 (n = 3)100/200 (n = 3)200/400 (n = 3)400/800 (n = 3)800/1200 (n = 3)1200/1200 (n = 3)1600/1600/ 800 (n = 3)All (N = 21)
    CR/CRu*111115
    PR11114
    SD1225
    PD21126
    Death11
    • PD indicates progressive disease.

    • * One patient with PR at the end of treatment later converted to CR.

    • One patient with PR after 4 cycles of treatment experienced disease progression before the end of treatment (8 cycles).

    • One patient who was stable at the end of treatment later converted to PR.

  • Table 5

    Response by FcγR polymorphisms (best overall response)

    FcγR IIaFcγR IIIa
    HR (n = 7)HH (n, 5)RR (n = 5)FF (n = 10)VV (n = 3)FV (n = 4)
    Responder, n (%)2 (29)3 (60)3 (60)5 (50)2 (67)1 (25)
    Nonresponder, n (%)5 (71)2 (40)2 (40)5 (50)1 (33)3 (75)
    • Response was defined as CR/CRu or PR; nonresponse was defined as progressive disease or SD. FcγR polymorphism data were available for 20 patients.