Expansion of Cirmtuzumab/Ibrutinib Study Shows Promise in MCL

Researchers have opened an expansion cohort to include patients with mantle cell lymphoma (MCL) in the phase I/II CIRLL study to determine if adding a tyrosine-protein kinase transmembrane receptor-1 (ROR1) antibody to ibrutinib (Imbruvica) can increase the rate of complete remissions.

While targets like rituximab (Rituxan) target CD20, the expression also targets normal B cells as well as abnormal malignant clone B cells. Meanwhile, ROR1 expression is found in malignant cells, especially in chronic lymphocytic leukemia (CLL) and MCL, according to Hun Ju Lee, MD.

“If we can find a target that is only expressed by malignant cells, then we will be able to target that without causing collateral damage to normal B cells. That's the holy grail of what we call targeted medicine-the target is only expressed by the neoplastic malignant cells and not the normal cells,” Lee, an associate professor of medicine, Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center in Houston, said in an interview with OncLive, CancerNetwork’s sister publication.

“If ROR1 is only expressed in CLL, MCL, Ewing sarcoma, breast cancer, etc., this will be a golden target that we can go after. If patients have CLL or MCL, they're not going through embryogenesis so this will not have an impact on the biological function of ROR1,” he added.

The combination of cirmtuzumab (UC-961) and ibrutinib has shown promise in patients with CLL: The overall response rate was 91.7% after 16 to 48 weeks of treatment, including 6 partial responses (PRs), 1 confirmed complete response (CR) with no morphologic evidence of CLL in the marrow, 1 clinical CR, and 4 cases of stable disease. Moreover, the combination has been well tolerated.

Therefore, the researchers have expanded the combination’s evaluation in patients with MCL. “I think that we will be able to show that we will get deeper remissions with the combination…. [Cirmtuzumab is] a complementary drug that has no overlapping toxicity and will be able to offer our patients a deeper remission and a longer duration of response,” Lee said.

Thus far, 6 patients with MCL are enrolled, 3 of which have experienced responses. In addition, there have been 2 CRs, 2 PRs, and 1 patient with progressive disease. 

“It's much more preliminary than the CLL cohort. However, the first patient with MCL who went on this trial that excited me was a patient who was a post-allogeneic transplant who failed allogeneic transplant and presented to me in my clinic with about an 8-cm size mass on the chest wall. After about 2 or 3 cycles of cirmtuzumab plus ibrutinib, he was able to get into CR by Lugano criteria,” Lee said.

The researchers recently finished the phase I dose-finding study. “I think that we will be able to show that we will get deeper remissions with the combination. I like to look at this like ibrutinib is Michael Jordan, and Jordan didn't win any championships until Scottie Pippen, Jr. came to the Chicago Bulls. I feel that cirmtuzumab is like Scottie Pippen, Jr. It's a complementary drug that has no overlapping toxicity and will be able to offer our patients a deeper remission and a longer duration of response,” Lee said, adding that the data will be presented at ASH 2019.

This article was adapted from an article that originally appeared on OncLive, titled “Cirmtuzumab/Ibrutinib Study Expands to Include Patients With MCL.”