A Study of Zilovertamab and Ibrutinib in Patients With Relapsed or Refractory Mantle Cell Lymphoma

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.