a study of zilovertamab and ibrutinib in patients with relapsed or refractory mantle cell lymphoma

Conditions: Lymphoma, Mantle-Cell; Lymphoma; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell

Summary: this is a phase 3 study to investigate the safety and efficacy of the investigational drug, zilovertamab, when given in combination with ibrutinib in patients with relapsed/refractory (r/r) mantle cell lymphoma (mcl).

this is a phase 3, multicenter, randomized, double-blind, placebo-controlled study that will be conducted in multiple phases in patients with r/r mcl. the study phases will include a screening phase, an open-label ibrutinib monotherapy treatment phase, a randomized double-blind treatment phase, and a long-term follow-up phase. when patients meet all study eligibility requirements in the screening phase, they will enter the open-label ibrutinib monotherapy treatment phase and will receive ibrutinib alone daily. after approximately 16 weeks patients who have a partial response (pr) or stable disease (sd) will enter the randomized double-blind treatment phase and will be receive an intravenous infusion of zilovertamab or placebo and will continue to receive ibrutinib daily. patients who discontinue study drug will enter the long-term follow-up phase.

Eligibility criteria:
inclusion criteria: * histologically confirmed mcl * has received one prior regimen for mcl * disease is relapsed or refractory * at least 1 measurable site of disease that is ≥ 2.0 cm * pet-ct performed less than 28 days before study entry * if a subject has toxicities due to prior therapy for the treatment of mcl, must be stable and recovered * eastern cooperative oncology group performance status of 0 or 1. * study-specific laboratory parameters must be met * females of childbearing potential and males must use highly effective contraception exclusion criteria: * received more than one month of prior therapy with ibrutinib or any other bruton's tyrosine kinase inhibitor * concurrent enrollment in another investigational study * transfusion-dependent thrombocytopenia * anticancer therapy within 25 days before the start of the study * history of other malignancy, cancer, or carcinoma for at least three years before the start of the study * central nervous system (cns) involvement with lymphoma * cns disorder ≤ 6 months of study entry * history of myocardial infarction, cardiac angioplasty or stenting, unstable angina, active arrhythmias, class 3 or 4 congestive heart failure, or other clinically significant cardiac disease ≤ 6 months of study entry * active or prior cardiac (atrial or ventricular) lymphoma involvement * history of atrial fibrillation or left or right bundle branch block * history of symptomatic deep vein thrombosis or pulmonary embolism ≤ 6 months of study entry * chronic liver disease with hepatic impairment, child-pugh class b or c * bleeding disorder * prior stem cell transplant that requires ongoing immunosuppressive therapy or active clinical graft versus host disease * primary severe immunodeficiency * human immunodeficiency virus infection (hiv) or active hepatitis b or c infection * active infection requiring iv antimicrobial (antiviral, antibiotic, anti-fungal) therapy at the time of study entry * vaccination with a live, attenuated vaccine ≤ 4 weeks of the start of the study * hypersensitivity reaction to any of the agents used in this study * requires treatment with a strong cytochrome p450 enzyme (cyp) 3a (cyp3a) inhibitor/inducer. * unable or swallow capsules or tablets or has malabsorption syndrome or disease affecting gastrointestinal function * major surgery ≤ 4 weeks of study start * medical condition likely to interfere with assessment of safety or efficacy of the study drug * not eligible in the opinion of the investigator * pregnant or breastfeeding other protocol-defined inclusion/exclusion criteria will apply.

Keywords: mantle cell lymphoma receptor tyrosine kinase-like orphan receptor 1 (ror1) bruton tyrosine kinase (btk) inhibitor ibrutinib zilovertamab