A Phase 1b/2 clinical trial evaluating Oncternal Therapeutics‘ investigational therapy cirmtuzumab in combination with Imbruvica (ibrutinib) for the treatment of B-cell malignancies has dosed its first patient with mantle cell lymphoma.
The trial is currently recruiting participants, including patients with mantle cell lymphoma (MCL) and chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL). Patients are eligible to apply if they received no prior treatment with BTK inhibitors such as Imbruvica.
The study is ongoing in four clinical sites in the U.S., including the MD Anderson Cancer Center in Houston, Texas, where the first MCL patient was dosed. A total of 117 patients are expected to enroll.
Oncternal is sponsoring this trial in close collaboration with researchers at the University of California San Diego School of Medicine and the California Institute for Regenerative Medicine.
The CIRLL study (NCT03420183) has two parts. In part 1, patients will receive a fixed dose of cirmtuzumab alone, followed by a combination of cirmtuzumab and Imbruvica. This phase will enroll up to 48 patients to determine the recommended dosing regimen to be tested in part 2.
In Phase 2, approximately 90 people with MCL will be randomized to receive cirmtuzumab plus Imbruvica at the recommended dose, or Imbruvica alone.
The trial’s main objectives are to determine the recommended dosing regimen (part 1) and compare the percentage of patients achieving a complete response in the combo therapy with that of Imbruvica alone.
Imbruvica is the standard of care for MCL patients who 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 blocking the ROR1 receptor in tumor cells. ROR1 is rarely seen in healthy cells but helps tumor cells grow by working as a receptor for the tumor growth factor Wnt5a. A recent study suggests that combining these two treatments produces significantly better results than either agent alone.
“There remains significant unmet medical need for patients with B-cell malignancies because current drug treatments can induce partial responses, but these are temporary. It is our hope that adding cirmtuzumab to standard of care ibrutinib will induce complete responses that may be durable,” James Breitmeyer, MD, PhD, Oncternal’s president and CEO, said in a press release.
“Our collaboration with Dr. Thomas Kipps of UC San Diego has shown that cirmtuzumab and ibrutinib synergistically block multiple signaling pathways that are important in the pathogenesis and progression of B-cell lymphomas and leukemias and provide a strong rationale for combination therapy,” he added.
