High Overall Response Rates Achieved With Cirmtuzumab/Ibrutinib in MCL and CLL

Hun Ju Lee, MD

The combination of cirmtuzumab and ibrutinib (Imbruvica) achieved high overall response rates (ORR) in patients with mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL) who were treated in a phase 1/2 study, according to findings from presented during the 2021 ASCO Annual Meeting.

The safety profile of the treatment regimen was also well tolerated, Hun Ju Lee, MD stated during the presentation.

“The majority of the patients demonstrated a significant reduction in tumor sizes,” lead study author Lee, assistant professor of medicine in the Department of Lymphoma & Myeloma at The University of Texas MD Anderson Cancer Center said during the presentation.

ORR for patients with MCL was 83.3% and was 91.1% for patients with CLL. The complete response rates were 38.9% and 14.7% for the MCL and CLL arms, respectively. Ultimately, 94.4% of patients with MCL and 100% of patients with CLL elicited a clinical benefit from the cirtuzumab/ibrutinib regimen.

The median progression free survival in both cancers was not reached.

Because MCL and CLL are considered incurable, the study aimed to test the efficacy and safety profile of cirmtuzumab, which inhibits tumor promoting activity of onco-embryonic tyrosine kinase receptor ROR1 found in many solid and hematologic cancers, plus ibrutinib in patients with relapsed/refractory MCL or treatment naïve or relapsed/refractory CLL.

The study was performed in 3 parts with separate arms. Part 1, for dose escalation; part 2, for dose expansion; and part 3, comparing cirmtuzumab plus ibrutinib with ibrutinib alone in CLL.

Overall, 26 patients with refractory MCL (median age 66.5, 15.4% women) and 34 patients with treatment naïve or RR CLL (median age 68, 23.5% women) were enrolled in the study.

For part 1, 12 patients with MCL were enrolled, and 5 into part 2. The median number of prior regimens was 2, including patients relapsing after ibrutinib (n=4), autologous stem-cell transplantation (n=3), autologous stem cell transplantation/allogenic stem cell transplantation (1) and autologous stem cell transplantation /CAR-T (1). For patients with CLL, at least 74% were high risk, as determined by unmutated IGHV, del17p and/or del11q, in parts 1 and 2.

In part 1, cirmtuzumab was given intravenously 5 times every 2 weeks, and then every 4 weeks, at 2 to 16 mg. Three-hundred or 600 mg doses were also examined. Researchers assessed the safety profile of cirmtuzumab during the first 28 days, which was then followed by ibrutinib at approved doses for each indication. A treatment regimen of cirmtuzumab (600 mg) given intravenously 3 times every 2 weeks, and then every 4 weeks, in combination with ibrutinib starting day 0, was chosen as the recommended dosing for parts 2 and 3.

“In summary, cirmtuzumab plus ibrutinib is a very well tolerated regimen,” Lee noted.

Adverse events with 20% or greater incidence were recorded, including fatigue (n=11), diarrhea (n=9), contusion (n=7), dizziness (n=7) and nausea (n=7). “The efficacy is robust in many of these pre-treated patients, [including] high response, rate durable response [and] encouraging PFS, demonstrating clinical benefit,” he concluded.

Of note, the phase 2 study for CLL is completed, and is awaiting a long-term follow-up. Phase 2 for MCL is currently enrolling.

_References

_{Lee HJ, Choi M, Siddiqi T, et al. Phase 1/2 study of cirmtuzumab and ibrutinib in mantle cell lymphoma (MCL) or chronic lymphocytic leukemia (CLL). J Clin Oncol. 2021;39(suppl 15; abstr 7556).}