On August 20, 2018 Cellectar Biosciences (Nasdaq: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported that data from Cohort 5 of the company’s ongoing Phase 1b clinical trial evaluating CLR 131 for the treatment of relapsed/refractory (R/R) multiple myeloma (MM) (Press release, Cellectar Biosciences, AUG 20, 2018, View Source [SID1234529088]).
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Unlike prior cohorts that used single doses of CLR 131, Cohort 5 utilized a fractionated two-dose regimen of 15.625 mCi/m2 given approximately one week apart. This dosing schedule provides higher average drug exposure but lower peak serum levels than non-fractionated dosing potentially reducing adverse events and improving efficacy. The independent Data Monitoring Committee (DMC) determined the fractionated dose used in Cohort 5 to be safe and well tolerated and recommended advancement to a higher dose cohort.
Results from Cohort 5 indicate enhanced tolerability and safety in comparison to Cohort 4 despite an 18% increase in total average dose from 55.29 mCi to 65.15 mCi of CLR 131. Patients in Cohort 5 required less supportive care such as transfusions of platelets or packed red blood cells than seen in previous cohorts. Based on the results and DMC recommendation, the company plans to initiate a sixth cohort using a fractionated dose regimen of two doses of 18.75 mCi/m2 administered one week apart and to modify the dosing regimen of its ongoing Phase 2 trial of R/R hematologic malignancies to use fractionated dosing.
In addition to the improved safety profile demonstrated in Cohort 5, the company also monitored signals of efficacy. Despite Cohort 5 patients averaging 5 lines of prior systemic therapies, all patients experienced clinical benefit with two patients achieving minimal responses and two stable disease. Furthermore, looking at surrogate markers, patients in Cohort 5 monitored by M-protein showed a nearly 50% further reduction in M-protein than seen in Cohort 4.
"We are encouraged with the potential for improving the CLR 131 profile with the fractionated dose regimen. These results point to the promise of this dosing strategy to increase efficacy and improve clinical outcomes," said James Caruso, president and chief executive officer of Cellectar Biosciences. "In the fight against cancer, dose-limiting toxicities are a critical challenge to achieving therapeutic efficacy. We believe the fractionated dose regimen and our targeted drug delivery may overcome this challenge and we plan to incorporate it into current and future trial designs."
About Phospholipid Drug Conjugates
Cellectar’s product candidates are built upon a patented delivery and retention platform that utilizes optimized phospholipid ether-drug conjugates (PDCs) to target cancer cells. The PDC platform selectively delivers diverse oncologic payloads to cancerous cells and cancer stem cells, including hematologic cancers and solid tumors. This selective delivery allows the payloads’ therapeutic window to be modified, which may maintain or enhance drug potency while reducing the number and severity of adverse events. This platform takes advantage of a metabolic pathway utilized by all tumor cell types in all cell cycle stages. Compared with other targeted delivery platforms, the PDC platform’s mechanism of entry does not rely upon specific cell surface epitopes or antigens. In addition, PDCs can be conjugated to molecules in numerous ways, thereby increasing the types of molecules selectively delivered. Cellectar believes the PDC platform holds potential for the discovery and development of the next generation of cancer-targeting agents.
About CLR 131
CLR 131 is Cellectar’s investigational radioiodinated PDC therapy that exploits the tumor-targeting properties of the company’s proprietary phospholipid ether (PLE) and PLE analogs to selectively deliver radiation to malignant tumor cells, thus minimizing radiation exposure to normal tissues. CLR 131 is in a Phase 2 clinical study in R/R MM and a range of B-cell malignancies and a Phase 1b clinical study in patients with R/R MM exploring fractionated dosing. The objective of the multicenter, open-label, Phase 1b dose-escalation study is the characterization of safety and tolerability of CLR 131 in patients with R/R MM. Patients in Cohorts 1-4 received single doses of CLR 131 ranging from 12.5 mCi/m2 to 31.25 mCi/m2. All study doses have been deemed safe and well tolerated by an independent Data Monitoring Committee. The company is currently initiating a Phase 1 study with CLR 131 in pediatric solid tumors and lymphoma, and is planning a second Phase 1 study in combination with external beam radiation for head and neck cancer.