Phase 3 Study to Evaluate Ibrutinib Plus Zilovertamab for R/R MCL Treatment

The phase 3 ZILO-301 study will evaluate the combination of zilovertamab and ibrutinib in patients with relapsed or refractory mantle cell lymphoma.

Zilovertamab (formerly cirmtuzumab or UC-961), an investigational, humanized, potentially first-in-class monoclonal antibody, is being investigated in combination with ibrutinib (Imbruvica) in a phase 3 study for patients with relapsed/refractory (r/r) mantle cell lymphoma (MCL), according to an announcement by Oncternal Therapeutics ZILO-301, NCT05431179).

Exploration of the novel combination is the result of a collaboration between Oncternal Therapeutics and the AbbVie subsidiary, Pharmacyclics. The agreement states that Pharmacyclics will provide ibrutinib for use in the study.

“This agreement represents a significant milestone for Oncternal as we advance towards the planned initiation of our registrational study ZILO-301 in the third quarter of 2022,” said James Breitmeyer, MD, PhD, Oncternal’s president and chief executive officer, in a press release.” “Ibrutinib was the first Bruton’s tyrosine kinase (BTK) inhibitor in the market and its approval changed the treatment paradigm for patients suffering from certain hematological malignancies. We are pleased that this collaboration will support the development of an innovative combination of zilovertamab and ibrutinib that we believe may address important unmet needs of patients with MCL.”

ZILO-301 is a phase 3, randomized, double-blind, placebo-controlled, multicenter study that will include 365 patients with r/r MCL. Patients will be randomized to be treated in 1 of 3 arms. In the first arm, patients will receive a 560-mg dose of ibrutinib alone. In arm 2, patients will receive the investigational combination of zilovertamab 600 mg and ibrutinib, and in arm 3, patients will receive placebo with ibrutinib.

The primary end point of ZILO-301 is progression-free survival. The study will also investigate objective response rate, duration of response, complete response rate, overall survival, and the overall safety profile of zilovertamab/ibrutinib as secondary end points.

To be eligible for inclusion in the study, patients must have a histological diagnosis of MCL that has been treated with 1 prior regimen. All patients must have relapsed or refractory disease, at least 1 measurable lesion, and an ECOG performance status of 0 or 1. PET-CT scan must have been performed less than 28 days before study entry. Patients with toxicities due to prior therapy for the treatment of MCL, must be stable and recovered before enrolling in the study, and study-specific laboratory parameters must be met. All patients must agree to use contraception throughout the study to be eligible for enrollment.

Patients are excluded from the study if they have received more than one month of prior therapy with ibrutinib or any other BTK inhibitor, are concurrently enrolled in another investigational study, received anticancer therapy within 25 days before the start of the study, underwent prior stem cell transplant that requires ongoing immunosuppressive therapy or active clinical graft versus host disease, or were vaccinated with a live, attenuated vaccine ≤ 4 weeks of the start of the study. The study also excludes individuals who have infections or other comorbidities that may interfere with the efficacy and safety of the study treatments.

REFERENCES:

1. Oncternal Therapeutics announces clinical trial collaboration to advance zilovertamab phase 3 study in combination with ibrutinib for patients with MCL. News release. July 14, 2022. Accessed July 19, 2022. https://bit.ly/3PH9lu2

2. A study of zilovertamab and ibrutinib in patients with relapsed or refractory mantle cell lymphoma. Clinicaltrials.gov. Updated June 24, 2022. Accessed July 19, 2022. https://clinicaltrials.gov/ct2/show/NCT05431179?term=Zilovertamab&draw=2&rank=3