Beleodaq (belinostat), an already approved drug for the treatment of peripheral T-cell lymphomas, has shown early promise in the treatment of other tumor indications when combined with immune checkpoint inhibitors, according to a recent announcement by Onxeo.
The preclinical studies conducted in a liver cancer mouse model, part of the second step of Onxeo’s preclinical development program, result from a collaboration with the University of Navarra’s University Clinic and Center for Applied Medical Research in Spain, led by Prof. Bruno Sangro and Dr. Pablo Sarobe.
In July 2014, the FDA approved Beleodaq to treat patients with relapsing or refractory peripheral T-cell lymphoma, a rare and fast-growing type of non-Hodgkin’s lymphoma, based on its tumor response rate and duration of response. The drug works by inhibiting histone deacetylases, preventing the T-cells from becoming cancerous.
Now, researchers have focused on the anti-tumor activity of Beleodaq in solid tumors. Preclinical data from Beleodaq in mice with hepatocellular carcinoma (liver cancer) that had a fully functional immune system, showed that combining this drug with immune checkpoint inhibitors resulted in a complete inhibition of tumor growth in 100 percent of the treated mice. This contrasted highly with the results seen when immune checkpoint inhibitors were given as monotherapy, which inhibited tumor growth in only 30 percent of treated mice.
Also, the tumor growth inhibition observed with the combination therapy lasted for nearly one week after Beleodaq administration.
The researchers found that this was associated with an underlying immune response, with increased production of proteins that regulate immune responses and lower numbers of regulatory T-cells (cells that inhibit the function of tumor-killing T-cells), compared to mice treated with checkpoint inhibitors alone.
“These data represent promising findings for the continued evaluation of Beleodaq in cancers beyond peripheral T-cell lymphoma (PTCL) when used as a combination with immuno-oncology agents in various tumor indications such as, for example, HCC,” Graham Dixon, PhD, chief scientific officer of Onxeo, said in a news release.
“Approximately 20 percent of cancer patients currently treated with checkpoint inhibitors alone are responding and thus, if translated into the clinic, the positive outcomes from the combination therapy would account for a significant improvement in the number of patients exhibiting high treatment responses,” he said.
“As a next step in our collaboration with Prof. Bruno Sangro and Dr. Pablo Sarobe, we are conducting follow-up studies to fully characterize these preclinical findings demonstrating the potential of Beleodaq in combination with checkpoint inhibitors in various tumor indications, and in particular, are evaluating the immune response in the tumor microenvironment in order to improve the translation of the response into human patients,” Dixon added.
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