CLOVER WaM Trial of Iopofosine I 131 Meets Primary End Point in WM

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The CLOVER WaM trial (NCT02952508) evaluating treatment with iopofosine I 131 for patients with relapsed/refractory Waldenstrom’s macroglobulinemia (WM) that have received at least 2 prior lines of therapy, including Bruton tyrosine kinase inhibitors (BTKi) met its primary end point with a major response rate (MRR) of 61% (95% CI, 44.50%-75.80%; 2-sided P <.0001).¹

Responses observed in the study were durable with an overall response rate of 75.6% in evaluable patients. All patients experienced disease control, the median duration of response was not reached, and at a median follow-up of 8 months, 76% of patients remained progression-free.

Further, these outcomes exceed real world data, which demonstrate a 4-12% MRR and a duration of response of approximately 6 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 in this highly refractory WM population.

"There is a critical need for new therapies with novel mechanisms of action to treat WM. There are no approved treatments for patients post BTKi therapy, where currently the expected response rate to salvage treatments is approximately 10%, and the expected duration of response in those patients is less than 6 months,” Sikander Ailawadhi, MD, professor of medicine at Mayo Clinic, and lead investigator in the CLOVER WaM study, said in a press release. “The results from this pivotal study utilizing just four doses of iopofosine monotherapy in heavily pretreated patients are very compelling, demonstrating deep and durable remissions. The combination of the safety profile and deep durable responses with a high proportion of patients remaining treatment free is impressive."

Iopofosine I 131 is a potential first-in-class, targeted radiotherapy candidate. Previously reported data has shown the agent to be well tolerated. Iopofosine I 131 is being evaluated in CLOVER WaM, the largest study to date in patients with relapsed or refractory WM post-BTKi therapy.

The single-arm CLOVER WaM trial is fully enrolled. Patients were required to have histologically or cytologically confirmed WM, an ECOG performance status of 0 to 2, a life expectancy of at least 6 months, and have received at least 2 prior lines of therapy for WM.²

With a data cut-off date of January 3, 2024, topline safety data is being reported on 45 patients who meet criteria for modified intent to treat (mITT).¹ The 41 patients in the efficacy evaluable population must have received a total administered dose of greater than 60 mCi and had follow-up of at least 60 days following treatment with their last dose.

The median age of the mITT patients was 71 years. The median IgM level prior to treatment with iopofosine was 2,185, and 90% of patients were refractory to either a BTKi (50%) or anti-CD20 therapy (40%). Further, 26.7% of patients were multiclass refractory, and 80% were previously treated with a BTKi.

Iopofosine I 131 had a toxicity profile consistent with previously reported safety data, and no treatment-related adverse events (TRAEs) led to discontinuation of treatment. Grade 3 or greater TRAEs which were seen in more than 10% of patients included thrombocytopenia (55%), neutropenia (37%), and anemia (26%). All patients recovered from cytopenias with no reported aplastic sequelae, there were no clinically significant bleeding events, and the rate of febrile neutropenia was 2%. Further, no treatment-related deaths were reported.

REFERENCES:

Cellectar Biosciences announces positive topline data achieving primary endpoint in pivotal clinical study of iopofosine I 131 in waldenstrom’s macroglobulinemia. News release. Cellectar Biosciences, Inc. January 8, 2024. Accessed January 8, 2024. http://tinyurl.com/yckf3hxy

Study of iopofosine I 131 (CLR 131) in select B-cell malignancies (CLOVER-1) and pivotal expansion in waldenstrom macroglobulinemia (CLOVER-WaM). ClinicalTrials.gov. Updated January 8, 2024. Accessed January 8, 2024. https://clinicaltrials.gov/study/NCT02952508