Cellectar Biosciences is expanding its Phase 1 dose-escalating trial to evaluate the effectiveness and safety of multiple administrations of CLR 131 for the treatment of relapsed or refractory multiple myeloma.
The trial’s fifth group of patients will receive two 15.625 mCl/m2 doses of CLR 131, one week apart. The combined dose (31.25 mCi/m2) is the same that resulted in a partial response when previously given as a single infusion in the fourth group.
“This fifth cohort represents an important opportunity to better understand the clinical utility of a split dose regimen and to further explore the safety and efficacy of CLR 131,” Jim Caruso, president and CEO of Cellectar Biosciences, said in a press release. “Clinical assessment, along with the improved benefits demonstrated by two doses in preclinical studies, suggest to us that the protocol changes should enhance our chances to see improved patient outcomes in this and future study arms.”
CLR 131 is a phospholipid drug conjugate (PDC) being developed for the treatment of blood cancers. It delivers a radioactive, toxic compound — iodine-131 — directly to cancer cells by targeting specific lipid molecules in their membrane.
The potential therapy is currently being evaluated in a dose-escalating Phase 1 trial (NCT02278315) in heavily treated multiple myeloma patients. To date, study participants were included in one of four dose groups, or cohorts, to determine the best and safest dosing regimen of CLR 131.
Data from the first group revealed that heavily treated patients (with an average of 5.8 prior treatments) receiving a single dose of CLR 131 lived for a median of 22 months. But those in the higher dose group demonstrated the best responses. All three patients benefited from treatment, including two who saw their disease stabilize and one who had a partial response.
Despite the promising results, recent preclinical data suggest that two or three doses might be better than a single dose at improving survival and reducing tumor burden. This prompted the company to expand the trial with a fifth group to study a multiple dose regimen of CLR 131.
Similar to the fourth group, the fifth will also include heavily pretreated relapsed or refractory patients who received more than five prior lines of therapy. Participants will be given CLR 131 as 30-minute infusions on days one and seven. Safety and effectiveness will be assessed during the next 85 days.
“Given the encouraging results we’ve observed to date in previous cohorts, we hope to see similar, or perhaps even improved safety results in this arm of the trial,” said Natalie Callander, MD, director of the University of Wisconsin Carbone Cancer Center Myeloma Clinical Program and lead investigator of the trial.
“Utilizing two doses provides an opportunity to increase the total amount of drug delivered to the patients which could result in an improvement in efficacy while maintaining similar or better safety profile,” Caruso said.