Dose-Limiting Toxicity Observation Phase Completed in CRS Trial for Lymphoma

In a phase 1b/2a trial for patients with blood cancers who have cytokine release syndrome (CRS), investigators have successfully completed dose-limiting toxicity observation period for the first patient group in its ongoing study, according to a news release from CytoAgents Inc.

Moreover, a Safety Review Committee, following the evaluation of safety and preliminary efficacy data, has authorized dose-escalation to the next planned, higher planned dose for cohort 2 of the investigational study.

The first-dosing cohort included in the clinical trial observed patients with diffuse large B-cell lymphoma (DLBCL) who were at risk for CRS while receiving CAR-T Cell therapy. In this patient group, current data showed a positive a favorable safety profile; there were no dose-limiting toxicities or drug-related serious side effects, and there was no interference with the patients' CAR-T cell therapy.

“This milestone marks an important step forward in our mission to deliver a safe, effective therapy for Cytokine Release Syndrome,” Teresa Whalen, CEO of CytoAgents, said in the news release. “We remain focused on advancing through the next stages of this trial and ultimately delivering a much-needed treatment option for patients facing this life-threatening immune response.”

“The safety and early efficacy data from the first dose cohort are encouraging,” Dr. Arthur P. Bertolino, chief medical officer of CytoAgents, noted in the news release. “We look forward to evaluating the higher dose cohorts to further study the potential of CTO1681 to prevent and treat CRS, a very significant toxicity of CAR T-Cell Therapy.”

More Information on the Phase 1b/2a Trial

The clinical trial is being conducted at multiple centers and is an open-label, dose-escalation study which is designed to evaluate the safety, tolerability and early effectiveness of the new investigational drug, CTO1681. The investigative agent is being explored in patients with DLBCL who are receiving CAR-T cell therapy and are at risk for CRS.

The study uses a standard approach, gradually increasing the dose to help determine the safest and most effective dose to use in future studies. Researchers are also evaluating the pharmacokinetics of CTO1681, as well as determining the recommended phase 2 dose. This means that how the body processes the drug and the best dose to move forward into the study with are both areas of interest which are being evaluated.

Of note, CTO1681 (the drug under investigation) is a new drug that is being developed and uses a novel approach to prevent or reduce CRS in patients receiving CAR-T cell therapy. According to the news release, the development of CRS represents an area of significant unmet medical need. This is because the majority of patients who receive treatment for their blood cancer with CAR-T cell therapy experience CRS and associated neurotoxicity.

What is Cytokine Release Syndrome (CRS)?

CRS, according to the Cleveland Clinic website, clevelandclinic.org, occurs in individuals when the immune system reacts too strongly to certain treatments, such as immunotherapy. This reaction causes the body to release large amounts of proteins called cytokines, which can lead affect multiple of your body’s organs. Symptoms of CRS can include fever, nausea, fatigue and body aches, creating an unmet need in the treatment space, and making prompt treatment key.

The Cleveland Clinic website goes on to say that CRS is most commonly seen in individuals undergoing immunotherapy for cancer, particularly treatments like CAR-T cell therapy or checkpoint inhibitors; however, it may also occur following viral infections. Individuals with autoimmune conditions or specific genetic syndromes may be more vulnerable to developing CRS.

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