Phase I Trial Aims to Evaluate Cobomarsen in Certain Hematologic Malignancies

New efficacy and safety data from the adult T-cell leukemia/lymphoma (ATLL) arm of the ongoing phase I clinical trial of cobomarsen was announced by miRagen Therapeutics, the agent’s developer. 

The data was presented at the 12th Annual T-Cell Lymphoma Forum in La Jolla, CA, which took place from January 30 to February 1, 2020. 

“We believe the results observed in prolonging survival in these types of ATLL patients with cobomarsen treatment are very promising,” Francine Foss, MD, professor of medicine in the Section of Medical Oncology at the Yale Cancer Center, said in a press release. “The prognosis for patients with residual disease after previous therapies is poor with few additional treatment options. Cobomarsen may provide long-term stabilization of disease with minimal side effects.”

The phase I trial is evaluating cobomarsen in cancers where the disease process appears to be correlated with an increase in miR-155 levels, including ATLL, diffuse large B-cell lymphoma, and chronic lymphocytic leukemia. 

The first 15 patients with aggressive subtypes of ATLL who were treated with 3 doses of cobomarsen by intravenous (IV) infusion at a dosage of 600, 900, and 1200 mg were reported on in the phase I ATLL arm of the study. Of the 15 in the cohort, 9 were actively relapsing at the time of screening and 6 had residual nodal or circulating leukemic disease after chemotherapy or other systemic therapies. For those 6 patients, the duration of cobomarsen treatment ranged from 4.5 to 23.7 months, with 3 patients still on the study as of October 17, 2019, the time of data analysis. 

Median survival time (MST) for the 6 patients was 26 months, compared with 7.4 months MST calculated from previous standard of care studies. Five of the 6 patients treated with cobomarsen were alive as of the data analysis. In the trial, disease stabilization was marked by an observed decrease in Ki-67, a biomarker of cell proliferation, as well as other biomarkers of cell activation on circulating tumor cells, providing evidence of the biological mechanism effect of cobomarsen on disease stabilization.

At the time of data analysis, there were 196 total reported adverse events (AEs) in patients given cobomarsen for ATLL, with only 22% of the total AEs considered possibly related to the study drug, and 86% of the total AEs considered mild or moderate. Fourteen percent of the total AEs, which were present in 8 patients, were grade 3 or 4 and most resolved within 11 days. With no drug related deaths and only 2 serious AEs occurring in the same patient and deemed possibly related to the study drug, the observed safety profile as of October 17, 2019 seems to be benign and well tolerated with chronic dosing.

“We believe that the survival, biomarker and safety data generated by this study is particularly notable as patients with aggressive ATLL historically have a poor prognosis,” William S. Marshall, PhD, president and CEO of miRagen, said in a press release. “We believe these data support the continued development of cobomarsen in ATLL, particularly as a maintenance therapy in those patients with residual disease after front-line therapy. This observed anticancer activity in patients with ATLL combined with our previously reported results in cutaneous t-cell lymphoma further strengthen our view that cobomarsen may be effective in the potential treatment of a variety of cancers where miR-155 is elevated.”

Marshall went on to indicate that in the second quarter of 2020 the company plans to request a meeting with the FDA to explore a potentially expedited development pathway for cobomarsen in ATLL. 

Reference:

miRagen Therapeutics Announces Positive Data for Cobomarsen in Adult T-Cell Leukemia/lymphoma Patients With Residual Disease [news release]. Boulder, Colorado. Published January 30, 2020. markets.businessinsider.com/news/stocks/miragen-therapeutics-announces-positive-data-for-cobomarsen-in-adult-t-cell-leukemia-lymphoma-patients-with-residual-disease-1028859116. Accessed January 31, 2020.