On February 19, 2020 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported positive data from its Phase 2 CLOVER-1 study in patients with relapsed/refractory B-cell lymphomas (Press release, Cellectar Biosciences, FEB 19, 2020, View Source [SID1234554481]). Additionally, the company announced the successful completion of its Phase 1 dose escalation study. Data from the studies demonstrated activity in all indications tested: multiple myeloma (MM), diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and lymphoplasmacytic lymphoma/Waldenstrom’s macroglobulinemia (LPL/WM).
Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:
Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing
Schedule Your 30 min Free Demo!
CLR 131 achieved notable response rates in patients with multiple myeloma – 34.5% overall response rate (ORR) over all therapeutic doses (n=33), and non-Hodgkin’s lymphoma (NHL) – 42% ORR over all doses (n=20) while maintaining a well-tolerated safety profile across all patients. Based upon these positive results and corroborating data showing the potential to further improve upon current overall response rates and durability of those responses, the study has been expanded to test a two-cycle dosing optimization regimen of CLR 131.
Patients in the studies were heavily pre-treated, with multiple myeloma patients having a median of five prior treatment regimens (range: 3 to 17), which included immunomodulatory drugs, proteasome inhibitors and CD38 antibodies for the majority of patients. Additionally, a majority of the patients (51%) were quad refractory or greater and 44% of all treated multiple myeloma patients were triple class refractory. NHL patients in the study were also heavily pre-treated, having had a median of 3 prior lines of treatment (range, 1 to 9) with the majority of patients being refractory to rituximab and/or ibrutinib. In both groups, the patients had a median age of 70 with a range of 51 to 86.
Relapsed/refractory multiple myeloma patients were treated with three different doses (<50mCi, ~50mCi and ~75mCi total body dose (TBD)); the <50mCi total body dose was a deliberately planned sub-therapeutic dose. Patients who received the highest dose of CLR 131 showed a 42.8% ORR, and those who received ~50mCi TBD had a 26.3% ORR with 100% of all evaluable patients (n=43) achieving clinical benefit (primary outcome measure) as defined by having stable disease or better. 85.7% of multiple myeloma patients receiving the higher total body dose levels of CLR 131 experienced tumor reduction. The 75mCi TBD demonstrated positive activity in both high-risk patients and triple class refractory patients with a 50% and 33% ORR, respectively.
"The data reported today are very promising and we believe the product profile for CLR 131 can improve further with the administration of a second cycle. These results are even more impressive considering the challenging patient population tested, as all were heavily pre-treated with the vast majority being refractory to their most recent therapy," said James Caruso, president and CEO of Cellectar Biosciences. "Based upon these compelling data and the need for new and innovative treatment options for patients, we plan to execute upon a well-defined and approvable regulatory path forward in a prioritized hematologic indication. We hope that this potentially first-in-class PLE-targeted radiotherapeutic will provide a new and meaningful treatment option for patients living with multiple myeloma and/or NHL."
The most frequently reported adverse events in relapsed/refractory multiple myeloma patients were cytopenias, which followed a predictable course and timeline. The most common grade ≥3 events at the highest dose (75mCi TBD) were hematologic toxicities including thrombocytopenia (65%), neutropenia (41%), leukopenia (30%), anemia (24%) and lymphopenia (35%). No patients experienced cardiotoxicities, neurological toxicities, infusion site reactions, peripheral neuropathy, allergic reactions, cytokine release syndrome, keratopathy, renal toxicities, or changes in liver enzymes. The safety and tolerability profile in patients with relapsed/refractory NHL was the same except for fewer cytopenias of any grade.
In addition to these findings, subtype assessments were completed in the r/r B-cell NHL patients. Patients with DLBCL demonstrated a 30% response rate with one patient achieving a complete response (CR), which continues at nearly 24 months post-treatment. The response rate for CLL/SLL/MZL patients was 33%. Only two mantle cell patients were enrolled, with stable disease as the best response.
Current data from the company’s Phase 2 CLOVER-1 clinical study show that four LPL/WM patients demonstrated 100% ORR with one patient achieving a complete response which continues at nearly 27 months. This may represent an important improvement in the treatment of relapsed/refractory LPL/WM as no approved or late-stage development treatments for second- and third-line patients have reported a complete response. LPL/WM is a rare, indolent and incurable form of non-Hodgkin’s lymphoma that is comprised of a niche patient population in need of new and better treatment options.
"For patients who have failed the current standard of care treatments for any of these indications, there is a need for additional treatment options," said lead study investigator Sikander Ailawadhi, M.D., Division of Hematology/Oncology, Department of Internal Medicine, Mayo Clinic, Jacksonville, Florida. He added, "These data are impressive, especially in these very difficult to treat patient populations. CLR 131 offers a very attractive safety and efficacy profile."
Conference Call Details
The management team will host a conference call for investors today, Wednesday, February 19 at 10:30 am Eastern Time to review the results and data from both the Phase 2 CLOVER-1 study and the Phase 1 r/r MM dose escalation study. The call will also include a presentation from lead investigator, Dr. Sikander Ailawadhi, M.D. Conference call, webcast and post-conference call replay details are as follows:
A webcast replay of the event will be available following the live event on the Events section of the Cellectar website.
About the Phase 2 CLOVER-1 Study
CLOVER-1 is a Phase 2 study of CLR 131 being conducted in approximately 10 leading cancer centers in the United States in patients with relapsed/refractory B-cell hematologic cancers. The hematologic cancers being studied include multiple myeloma (MM), chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), lymphoplasmacytic lymphoma/ Waldenstrom’s macroglobulinemia (LPL/WM), marginal zone lymphoma (MZL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL).
The study could enroll up to 80 patients with its primary endpoint being clinical benefit response (CBR), which is defined as the proportion of MM patients within three months following the initial infusion of CLR 131 with stringent complete response, complete response, very good partial response, partial response and stable disease per International Myeloma Working Group criteria, or the proportion of lymphomas patients (CLL/SLL, LPL, MZL, MCL, and DLBCL) within three months following the initial infusion of CLR 131 with CR, PR and SD per the Lugano classification CT-based response criteria. Additional endpoints include overall response rate (ORR), progression free survival (PFS), median overall survival (OS) and other markers of efficacy. Patients were treated with three different doses (<50mCi, ~50mCi and ~75mCi total body dose) administered in either a single 30-minute infusion or two 30-minute infusions at day 1 and day 7 (± 1), with the option for a second dose cycle approximately 75-180 days later.
Based upon positive results and corroborating data showing the potential to further improve upon the current overall response rates and durability of those responses, the study has been expanded to test a two-cycle dosing optimization regimen of CLR 131. Patients will be administered a two-cycle regimen with a total of four infusions, to be administered on day 1 and day 15 (± 1) and again on day 57 and day 71 (± 1).
Cellectar was awarded approximately $2 million in non-dilutive grant funding from the National Cancer Institute to help fund the study. More information about the study, including eligibility requirements, can be found at www.clinicaltrials.gov, reference NCT02952508.
About the Phase 1 r/r MM Dose Escalation Study
The Phase 1 multicenter, open-label, dose-escalation study is designed to evaluate the safety and tolerability of CLR 131 administered as a 30-minute I.V. infusion, either as a single bolus dose or as two fractionated doses. The r/r multiple myeloma patients in this study received doses ranging from ≤25mCi to ~75mCi total body dose. To date, an independent Data Monitoring Committee determined that all doses have been safe and well-tolerated by patients.
About CLR 131
CLR 131 is a small-molecule Phospholipid Drug Conjugate designed to provide targeted delivery of iodine-131 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 two Phase 1 dose-escalating clinical studies, one in multiple myeloma and one in pediatric solid tumors and lymphoma. The FDA granted CLR 131 Fast Track Designation for both r/r multiple myeloma and r/r DLBCL and Orphan Drug designation (ODD) for the treatment of multiple myeloma, lymphoplasmacytic lymphoma/Waldenstrom’s macroglobulinemia, 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. Most recently, the European Commission granted an ODD for r/r multiple myeloma.