On November 5, 2020 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported CLR 131 has demonstrated preliminary activity in inoperable brain tumors in a Phase 1 study (Press release, Cellectar Biosciences, NOV 5, 2020, View Source [SID1234570166]). The study is an international, open-label, dose escalation, safety study of CLR 131 in children and adolescents with relapsed or refractory cancers, specifically high grade gliomas (HGGs), high risk neuroblastomas and select soft tissue sarcomas.
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Highlights from the study:
-Four dose levels (15, 30, 45 and 60mCi/m2 ) have been evaluated to date with all deemed safe and tolerated by the independent Data Monitoring Committee; patients are currently being evaluated at the 75mCi/m2 dose level
-Initial activity was expected to occur at doses of 60mCi/m2 and higher; activity has been noted at lower dose levels
-CLR 131 has been measured in tumors, confirming that systemic administration of CLR 131 crosses the blood brain barrier and is delivered into tumors
-Disease control has been exhibited in heavily pretreated patients with ependymomas
"CLR 131’s ability to cross the blood brain barrier along with the initial responses in pediatric brain tumors are most encouraging. CLR 131 may provide an attractive new treatment option for these patients beyond the current paradigms of external beam radiation and/or systemic targeted radiation as standards of care," said Dr. John Friend, CMO of Cellectar. "These ultra-orphan pediatric indications align with the development and regulatory strategy that we have successfully employed with our lead program in heme-oncology. We look forward to providing feedback from our recent FDA Guidance meeting, outlining the registrational pathway for our priority adult hematology indications and planned initiation of our pivotal trial later in the fourth quarter."
Similar to previous CLR 131 studies in adults, this study demonstrated that 20-40% of the infused CLR 131 is delivered to the tumors. Additionally, the study demonstrated that systemic administration of CLR 131 results in a sufficient proportion of infused drug crossing the blood brain barrier and is delivered to different types of malignant brain tumors. CLR 131 has achieved disease control at multiple dose levels in rapidly progressing, heavily pretreated patients, including two patients at distinct dose levels with rapidly growing ependymomas. Pediatric HGGs are a collection of aggressive brain and central nervous system tumor subtypes (i.e. diffuse intrinsic pontine gliomas, glioblastomas, astrocytomas, ependymomas, etc.) with about 400 new pediatric cases diagnosed annually in the United States. Children with these tumors have a poor prognosis and limited 5 year survival.
It is noteworthy that CLR 131 is currently being dosed at 75mCi/m2 and when compared to another targeted radiotherapeutic, MIBG-Iodine-131 (second line standard of care in neuroblastoma), CLR 131 achieves a nearly 16 fold increase in the amount of radiation delivered to the tumor. This enhanced delivery suggests that doses of CLR 131 between 60 and 75mCi/m2 would be predicted to achieve similar responses in patients as an MIBG-Iodine-131 dose of up to 1,300mCi. Neuroblastoma is a cancer type that occurs in immature nerve cells of the adrenal gland, neck, chest or spinal cord with approximately 800 new cases diagnosed per year in the United States. Over 60% of the newly diagnosed cases of neuroblastoma are advanced with at least one site of metastasis resulting in a poor patient prognosis.
About CLR 131
CLR 131 is a small-molecule Phospholipid Drug Conjugate designed to provide targeted delivery of iodine-131 (radioisotope) directly to cancer cells, while limiting exposure to healthy cells unlike many traditional on-market treatment options. CLR 131 is the company’s lead product candidate and is currently being evaluated in a Phase 2 study in B-cell lymphomas, and a Phase 1 dose-escalating clinical study in pediatric solid tumors and lymphomas. The company recently completed a Phase 1 dose-escalation clinical study in relapsed/refractory (r/r) multiple myeloma. The U.S. Food and Drug Administration (FDA) granted CLR 131 Fast Track Designation for both r/r multiple myeloma and r/r diffuse large B-cell lymphoma and Orphan Drug Designation (ODD) for the treatment of multiple myeloma, lymphoplasmacytic lymphoma (LPL)/Waldenstrom’s macroglobulinemia (WM), neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. CLR 131 was also granted Rare Pediatric Disease Designations for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. Earlier this year, the European Commission granted an ODD for r/r multiple myeloma and most recently, the FDA granted Fast Track Designation for CLR 131 in LPL/WM in patients having received two prior treatment regimens or more.