Cellectar Biosciences, Inc. announced data from its CLOVER WaM pivotal study, evaluating iopofosine I 131, a potential first-in-class, targeted radiotherapy candidate for the treatment of relapsed/refractory Waldenstrom?s macroglobulinemia (WM) patients that have received at least two prior lines of therapy, including Bruton tyrosine kinase inhibitors (BTKi). CLOVER WaM is the largest study to date in relapsed or refractory WM patients post-BTKi therapy and represents the most refractory population ever tested in clinical studies based upon a review of published literature. The CLOVER WaM study met its primary endpoint with a major response rate (MRR) of 61% (95% confidence interval [44.50%, 75.80%, two-sided p value < 0.0001]).

The overall response rate (ORR) in evaluable patients was 75.6%, and 100% of patients experienced disease control. Responses were durable, with median duration of response not reached and 76% of patients remaining progression free at a median follow-up of eight months. These outcomes exceed real world data, which demonstrate a 4-12% MRR and a duration of response of approximately six months or less despite continuous treatment in a patient population that is less pretreated and less refractory to multiple classes of drugs.

Notably, iopofosine monotherapy achieved an 8% stringent complete remission (sCR) in this highly refractory WM population. CLOVER WaM is a single-arm registration study with a target enrollment of 50 patients. The study is fully enrolled and topline safety data is being reported on 45 patients meeting criteria for modified intent to treat (mITT) with a data cut-off date of January 3, 2024.

Topline efficacy evaluable population (41) is defined as patients who have received a total administered dose of greater than 60 mCi and had follow up of at least 60 days post last dose. Among mITT patients, median age was 71 years, median IgM level prior to treatment with iopofosine was 2,185, 90% were refractory to either a BTKi (18/36 50%) or anti-CD20 therapy (18/41 40%), with 26.7% multiclass refractory, and 80% of patients were previously treated with a BTKi therapy. Iopofosine I 131 was well tolerated and its toxicity profile was consistent with the Company's previously reported safety data.

There were no treatment-related adverse events (TRAEs) leading to discontinuation. The rates of Grade 3 or greater TRAEs observed in more than 10% of patients included thrombocytopenia (55%), neutropenia (37%), and anemia (26%). All patients recovered from cytopenias with no reported aplastic sequalae.

Importantly, there were no clinically significant bleeding events, and the rate of febrile neutropenia was 2%. There were no treatment related deaths in the study.