Iopofosine I 131 Shows Activity in Post-BTKi Waldenström Macroglobulinemia

Iopofosine I 131 demonstrated clinical activity in patients with relapsed or refractory Waldenström macroglobulinemia (WM) previously treated with Bruton tyrosine kinase inhibitors (BTKis), according to a subgroup analysis of the phase 2b CLOVER WaM trial (NCT02952508).¹

The subgroup analysis included patients who received a BTKi-containing regimen immediately before iopofosine I 131. Three-quarters of patients were refractory to BTKi therapy, and more than 54% had received multiple BTKi therapies. Patients had received a median of 3 prior lines of therapy, with a range of 2 to 7 lines.

Among 24 patients who received iopofosine I 131 immediately after a BTKi-containing regimen, the overall response rate was 87.5%, the major response rate was 79.2%, and the clinical benefit rate was 100%. Median duration of response was 16.0 months, and median treatment-free survival was 19.1 months.

Regarding safety, treatment-emergent adverse events occurred in fewer than 10% of patients in the subgroup. Cytopenias were the only treatment-emergent adverse events of grade 3 or higher reported in the analysis.

“These compelling data further strengthen the growing body of evidence supporting the potential of iopofosine I 131 to address a critical unmet need and offers something WM patients rarely get after BTKis: deep, durable responses from a short, fixed course of treatment. Because its targeted radiation works independently of the BTK pathway and other pathways currently targeted or attempting to be targeted, we believe it has the potential to remain effective as patients become refractory to today’s targeted therapies, and those still to come,” Jarrod Longcor, chief operating officer of Cellectar Biosciences, stated in a news release. “Patients in the immediate post-BTKi setting often face limited treatment options and increasingly refractory disease, making the robust response rates, durable clinical benefit, and favorable tolerability profile observed in this analysis especially encouraging.”

About CLOVER WaM and Prior Data

Iopofosine I 131 is an investigational radiopharmaceutical that uses iodine-131 to deliver targeted radiation to cancer cells through Cellectar's proprietary phospholipid drug conjugate platform. Its mechanism of action differs from that of BTKis, which may be relevant for patients whose disease is refractory to BTKi therapy.

CLOVER WaM is an open-label, multicenter, phase 2b study evaluating intravenous iopofosine I 131 in patients with relapsed or refractory WM who have received at least 2 prior lines of therapy.² The study's primary end point is major response rate (MRR), with duration of response and treatment-free survival among the secondary efficacy end points.

The trial met its primary end point with an MRR of 61%(95% CI, 44.50%-75.80%; 2-sided P <.0001) in the broader per-protocol population of 55 patients with at least 12 months of follow-up. A more recent report released in May 2026 showed an MRR of 61.8% and overall response rate of 83.6% in this population.

A Forthcoming Phase 3 Trial and Regulatory Plans

The sponsor is advancing plans for a randomized, confirmatory phase 3 trial evaluating iopofosine I 131 in patients with WM following first-line treatment and BTKi therapy. Progression-free survival is expected to serve as the primary end point. The sponsor reported that trial initiation and site selection were underway, with dosing of the first patients anticipated in the first quarter of 2027.

The sponsor has also reported plans to submit a new drug application to the FDA for accelerated approval in the first half of 2027. The regulatory strategy is based on the CLOVER WaM data, including major response rate supported by duration of response, with the confirmatory trial intended to further evaluate clinical benefit.

The findings from the post-BTKi subgroup add to the evidence supporting continued evaluation of iopofosine I 131 in patients with relapsed or refractory WM, including those whose disease is refractory to BTKi therapy. However, the analysis included a limited number of patients and did not include a comparator group. Results from the planned randomized phase 3 trial will be important for determining how iopofosine I 131 compares with other treatment options and whether its clinical activity translates into improved outcomes in this population.

REFERENCES

1. Cellectar Biosciences Presents Compelling Efficacy Data from Phase 2b CLOVER WaM Subset Analysis of Iopofosine I 131 in Patients Relapsed/Refractory to BTK Inhibitor Therapy at the International Workshop for Waldenström Macroglobulinemia. News release. Cellectar Biosciences. October 15, 2026. Accessed October 16, 2026. https://tinyurl.com/ynbxma72

2. Study of Iopofosine I-131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) With Expansion in Waldenstrom (CLOVER-WaM). ClinicalTrials.gov. Updated March 18, 2026. Accessed October 16, 2026. https://clinicaltrials.gov/study/NCT02952508