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

Oncternal Therapeutics

Status and phase: Withdrawn; Phase 3

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

Treatments: Drug: Zilovertamab; Drug: Placebo; Drug: Ibrutinib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05431179

ZILO-301

Details and patient eligibility

About

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).

Full description

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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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0 participants in 3 patient groups, including a placebo group

Oral Ibrutinib

Experimental group

Description:

Open Label Ibrutinib Monotherapy Phase (16 weeks)

Treatment:

Drug: Ibrutinib

Arm A: IV Infusion of Ziloveramab and Oral Ibrutinib

Experimental group

Description:

Randomized, Double-Blind Treatment Phase

Treatment:

Drug: Ibrutinib

Drug: Zilovertamab

Arm B: IV Infusion of Placebo and Oral Ibrutinib

Placebo Comparator group

Description:

Randomized, Double-Blind Treatment Phase

Treatment:

Drug: Ibrutinib

Drug: Placebo