A Phase 1/2 trial assessing Oncternal Therapeutics‘ cirmtuzumab plus Imbruvica (ibrutinib) for the treatment of B-cell cancers is opening a Phase 1b extension part to continue studying the combination in people with mantle cell lymphoma (MCL), the company announced.
The expansion was based on positive interim results from the trial’s dose-finding part, in which the therapy was well-tolerated and induced complete responses in two heavily-treated MCL patients who had failed multiple prior treatments.
The CIRLL trial (NCT03088878) is recruiting participants with MCL or chronic lymphocytic leukemia/small lymphocytic leukemia (CLL/SLL) at several U.S. sites, including centers in New York, Texas, Connecticut, Ohio, and California. The study aims to enroll a total of 156 patients ages 18 and older.
Imbruvica, developed by Janssen and AbbVie, is the standard of care for people with MCL who received at least one prior therapy. The molecule binds permanently to the Bruton’s tyrosine kinase protein, which is key for 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 helps tumor cells grow by working as a receptor for a certain tumor growth factor. Studies suggest that a combination of these two treatments produces significantly better results than either agent alone.
The open-label randomized CIRLL study was designed to assess the combination in two parts. The dose-finding part included CLL/SLL or previously treated MCL patients — who had not received prior BTK inhibitors — to determine the best dosing regimen for additional studies.
Then, the Phase 2 part would include an additional 90 people with CLL/SLL and randomly assign them to receive the recommended dose of cirmtuzumab plus Imbruvica or Imbruvica alone.
However, the promising findings from the first part led researchers to include an additional escalation group of MCL patients. That led to the early opening of the Phase 2 part for individuals with CLL/SLL.
The dose-finding portion included six people with MCL. Interim data presented at the 2019 ASCO Annual Meeting in June showed that one of these patients achieved a complete response after three months of treatment. That response included the disappearance of a large mass in the individual’s mediastinum — the part of the chest that separates the lungs, containing the heart, esophagus, thymus, and trachea — despite prior relapse after a stem cell transplant. This complete response was still ongoing after 12 months of treatment.
Later, a second patient whose disease progressed after several chemotherapy regimens, stem cell transplant, and CAR-T therapy also achieved a complete response.
“It is encouraging to see that the drug has been well tolerated as well as the early signal of efficacy of cirmtuzumab with ibrutinib in MCL, particularly the rapid and durable complete responses of the heavily pre-treated patients after three months of therapy, which is an unusually fast response in this patient population,” Hun Lee, MD, assistant professor of medicine at the University of Texas MD Anderson Cancer Center and an investigator on the CIRLL clinical trial, said in a press release.
Data from these patients will be shared at a future medical conference, the release said.
“We are pleased to be opening the expansion cohort portion of the CIRLL clinical trial for patients with MCL, and continue to be encouraged by the interim results from this study for both patients with MCL and patients with chronic lymphocytic leukemia, for whom a randomized Phase 2 portion of the trial was opened in August,” added James Breitmeyer, Oncternal’s president and CEO.