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INTEGRATED SAFETY DATA WITH COPANLISIB MONOTHERAPY FROM PHASE I AND II TRIALS IN PATIENTS WITH RELAPSED INDOLENT NON‐HODGKIN'S LYMPHOMA
Author(s) -
Zinzani P.,
Dreyling M.,
Patnaik A.,
Morschhauser F.,
Benson A.,
Genvresse I.,
Miriyala A.,
GarciaVargas J.,
Childs B.H.
Publication year - 2017
Publication title -
hematological oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 44
eISSN - 1099-1069
pISSN - 0278-0232
DOI - 10.1002/hon.2438_141
Subject(s) - medicine , neutropenia , adverse effect , meddra , obinutuzumab , febrile neutropenia , tolerability , common terminology criteria for adverse events , lymphoma , gastroenterology , nausea , phases of clinical research , follicular lymphoma , clinical trial , surgery , rituximab , toxicity , pharmacovigilance
relapsed disease. Obinutuzumab has increased antibody dependent cellular cytotoxicity (ADCC) compared to rituximab in preclinical models and is approved for FL. We hypothesized that the immunologic properties of obinutuzumab and lenalidomide would be synergistic in relapsed FL. The study's objectives were to determine the MTD of lenalidomide with obinutuzumab and describe the efficacy of the combination. Methods: This open label phase I/II study enrolled relapsed/refractory Gr 1–3a FL. Exclusions included transformation, prior malignancy, and infection. Lenalidomide was given on D 2–22 with 1000 mg obinutuzumab on D1, 8, 15, and 22 of cycle 1 and monthly on D 1 for up to 12 cycles. Extended dosing with obinutuzumab was given every 2 months thereafter for up to 30 months total in patients (pts) who responded following doublet therapy. During phase I, three escalating dose levels were planned with 10, 15, and 20 mg of lenalidomide. Phase II planned to enroll 30 pts at MTD with efficacy and safety as primary endpoints. Results: All 36 pts with FL enrolled (6 in dose escalation and 30 at MTD), and all are eligible for efficacy and safety analysis. The median age was 65 with a median of 2 prior therapies. No DLTs were observed in phase I, and 20 mg of lenalidomide was used for the phase II dose. To date, the most common all grade non‐hematologic toxicities included fatigue (83%), diarrhea (67%), and rash (53%). Grade 3+ toxicities included neutropenia (23%), infection (11%), and fatigue (8%). The overall response rate was 100% with 78% (95% CI: 60.85–89.88%), of pts attaining complete remission (CR/Cru). At a median follow up of 14 months, 10 pts progressed. The estimated 24 month PFS is 61% (95% CI: 43–87%). Conclusions: Lenalidomide and obinutuzumab is highly active with durable remissions in relapsed FL, with all pts responding and 78% achieving CR. The majority of pts remain on therapy and the combination appeared safe. Correlatives are ongoing to identify biomarkers of response and frontline studies of the combination are currently enrolling.