Following promising early efficacy results for a cirmtuzumab–Imbruvica treatment combo, a Phase 2 clinical trial has now been opened to people with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL).
The opening of this randomized trial was based on the promising results seen in the prior Phase 1 stage, in which 100% of the first nine CLL/SLL patients responded to treatment with Oncternal Therapeutics‘ investigational therapy cirmtuzumab in combination with Imbruvica (ibrutinib).
The Phase 2 clinical trial is now open to an additional 90 patients with CLL/SLL. Participants will be randomly selected to receive the combination of cirmtuzumab plus Imbruvica, or Imbruvica alone. More information on enrollment can be found on the trial’s page here.
Imbruvica, by Janssen and AbbVie, is the standard of care for people with CLL/SLL and mantle cell lymphoma (MCL) who have received at least one prior therapy. The molecule binds permanently to the Bruton’s tyrosine kinase protein, which is key in the growth and proliferation of B-cell cancers.
Cirmtuzumab is an antibody that blocks the ROR1 receptor in tumor cells. ROR1 is rarely seen in healthy cells, but in tumor cells it works as a receptor for growth signals, helping the tumor grow and survive.
Researchers have been testing a combination of these two treatments in patients with CLL/SLL and MCL who have failed prior therapies but have not received a prior BTK inhibitor.
The CIRLL Phase 1b/2 trial (NCT03420183) was first designed in three parts. First, participants received ascending doses of cirmtuzumab alone, followed by a combination of cirmtuzumab and Imbruvica. The goal was to determine the optimal dosing regimen for further testing.
The recommended dosing regimen then was further tested in part 2 (Phase 1b). In total, 66 patients were included in these two Phase 1 parts.
Preliminary data from these parts were presented in a poster, “Phase 1/2 Trial of Cirmtuzumab and Ibrutinib: Planned Analysis of Phase 1 CLL Cohorts,” at the American Society of Clinical Oncology (ASCO) annual meeting, held in the spring in Chicago.
The analysis included the first 12 CLL/SLL patients, for whom the treatment was safe and well-tolerated. The therapy led to an objective response rate of 91.7%. Three of the 11 patients who responded had clinical or confirmed complete responses.
Researchers noted that all nine patients who completed 12 weeks of treatment in part 2 — in which participants received a recommended dose of 600 mg cirmtuzumab plus 420 mg Imbruvica — achieved a response to treatment.
Preliminary data also was presented for the first six MCL patients. One participant, whose disease had returned after a stem cell transplant, had a complete response after three months of treatment, which was maintained at least until month 11. The treatment also led to the resolution of a tumor in the chest.
The findings in CLL/SLL participants led researchers to open a third part (Phase 2), to compare the safety and efficacy of the combination versus Imbruvica alone. The main goal is to compare the percentage of patients achieving a complete response.
“We are very pleased to be opening the randomized Phase 2 portion of the CIRLL study for patients with CLL and continue to be encouraged by the interim results from the study for both patients with CLL and patients with mantle cell lymphoma,” James Breitmeyer, MD, PhD, president and CEO of Oncternal, said in a press release.