Gazyvaro

Chronic lymphocytic leukemia (CLL) — previously untreated, in combination with chlorambucil; Follicular lymphoma (FL) — in combination with bendamustine followed by obinutuzumab monotherapy for patients who relapsed after or are refractory to a rituximab-containing regimen; FL — in combination with chemotherapy (bendamustine, CVP, or CHOP) followed by obinutuzumab monotherapy in previously untreated Stage II bulky, III, or IV patients who achieve at least a partial remission.

CLL (Cycle 1): Day 1: 100 mg IV, Day 2: 900 mg IV, Day 8: 1,000 mg IV, Day 15: 1,000 mg IV. Cycles 2-6: 1,000 mg Day 1 of each 28-day cycle
FL (relapsed): 1,000 mg IV on Days 1, 8, 15 of Cycle 1; Day 1 of Cycles 2-6 (with bendamustine); then 1,000 mg q2mo maintenance for 2 years
Pre-medication: Acetaminophen + antihistamine + glucocorticoid (dexamethasone 20 mg or methylprednisolone 80 mg)

Injection: 25 mg/mL (1,000 mg/40 mL) single-dose vial

None listed.

• Infusion-Related Reactions: Occurred in 69% of CLL patients during first infusion (21% Grade 3-4). Pre-medicate. Interrupt for any severity; discontinue for Grade 4 or recurring Grade 3.
• Tumor Lysis Syndrome: Reported within 12-24 hours of first infusion. Pre-medicate with anti-hyperuricemics and hydration.
• Infections: Fatal bacterial, fungal, and new or reactivated viral infections reported. Grade 3-4 in 12%.
• Neutropenia: Grade 3-4 in 40%. Late-onset neutropenia (>28 days after last dose) and prolonged neutropenia reported. Consider G-CSF prophylaxis.
• Thrombocytopenia: Grade 3-4 in 15%. Fatal hemorrhagic events during Cycle 1 reported.

Infusion-related reactions (69%), neutropenia (40%), thrombocytopenia (15%), nausea (37%), pyrexia (18%), cough (17%), diarrhea (17%), musculoskeletal pain (17%), fatigue (14%), constipation (12%), upper respiratory tract infection (11%)

Consult the complete prescribing information for a comprehensive list of adverse reactions and their frequencies.

Consult the complete prescribing information for drug interactions, including effects on CYP enzymes, transporters, and concomitant medications that may require dose adjustments or monitoring.

Consult the full prescribing information for pregnancy-related considerations.

Refer to prescribing information for lactation guidance.

Pediatric safety and efficacy information is detailed in the full label.

Dose modifications for organ impairment are specified in the complete prescribing information.

Obinutuzumab is a humanized, glycoengineered Type II anti-CD20 monoclonal antibody. The Fc portion is glycoengineered with a non-fucosylated carbohydrate, which results in enhanced binding to FcγRIIIa on immune effector cells. Compared to Type I anti-CD20 antibodies (rituximab), obinutuzumab induces greater direct cell death via a non-apoptotic lysosome-dependent mechanism, enhanced antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), but less complement-dependent cytotoxicity (CDC).

Half-life: approximately 28 days (after 1000 mg dose). Clearance decreases over time as CD20-positive B cells are depleted. Vd: approximately 3.8 L. Steady-state reached during Cycle 3 of treatment.

Clinical efficacy and safety data supporting the approval are available in the full prescribing information and from the clinical trials listed below.

• CLL11 — Obinutuzumab + chlorambucil vs. rituximab + chlorambucil vs. chlorambucil in 1L CLL. Phase III, n=781.
  🔬 NCT01010061 ↗ 📄 Primary Publication ↗

Gazyvaro has FDA-approved indications across the following cancer types covered on PipelineEvidence: