Cellectar's iopofosine I 131 shows durable WM responses at 12 months

Cellectar Biosciences has reported mature 12-month follow-up data from its Phase 2b CLOVER WaM trial of iopofosine I 131 in relapsed or refractory Waldenström macroglobulinemia (WM), meeting both its primary and secondary endpoints and reinforcing the company's case for an accelerated approval submission to the US Food and Drug Administration.

The per-protocol population of 55 patients — one of the most heavily pretreated WM cohorts studied to date, with a median of four prior lines of therapy — achieved an overall response rate of 83.6% and a major response rate (MRR) of 61.8%, the primary endpoint. Median duration of response reached 17.8 months, with median progression-free survival of 13.5 months. Disease control was achieved in 98.2% of patients. Notably, iopofosine I 131 is administered as a fixed four-infusion regimen rather than a continuous oral therapy, a scheduling profile the company positions as a differentiator.

Activity in post-BTKi patients

With Bruton tyrosine kinase inhibitors (BTKi) now standard of care in the frontline WM setting, post-BTKi outcomes carry considerable clinical weight. Among the 39 BTKi-exposed patients in CLOVER WaM, iopofosine I 131 achieved an MRR of 64.1%, a median duration of response of 18.2 months, and median PFS of 15.9 months — figures broadly comparable in the 33-patient BTKi-refractory subgroup. There are currently no FDA-approved options for patients progressing on BTKi therapy, a gap that Cellectar argues iopofosine could directly address.

James Caruso, president and chief executive officer of Cellectar, said the dataset "further strengthens the compelling clinical profile" of the candidate and that "the durability of response continues to improve over time." The safety profile was described as manageable, with cytopenias as the most common treatment-emergent event; the company reports no significant bleeding events and infection rates below 10%, contrasting with some currently approved WM therapies.

The FDA had specifically requested minimum 12-month follow-up across all enrolled patients before Cellectar advances its regulatory submission. With that dataset now complete, the company says it is preparing an accelerated approval filing based on MRR as a surrogate endpoint reasonably likely to predict clinical benefit. A confirmatory randomised study evaluating progression-free survival is planned to start in the fourth quarter of 2026. Data from patients treated immediately after BTKi therapy have been accepted for presentation at the American Society of Clinical Oncology Annual Meeting in Chicago at the end of May 2026.

Regulatory and competitive context

Accelerated approval in rare haematological malignancies remains an active pathway at the FDA, though the agency has in recent years signalled tighter expectations around surrogate endpoint validation and confirmatory trial readiness. The completion of 12-month follow-up on all patients, and the consistency of responses across subgroups, should help address those concerns in Cellectar's submission package.

WM is a rare B-cell lymphoma with approximately 26,000 prevalent cases in the United States, of which the company estimates roughly 5,700 are eligible for third-line or later treatment. That market is small in absolute terms but commands orphan drug pricing dynamics. Iopofosine I 131 already holds FDA Breakthrough Designation and six Orphan Drug Designations, as well as EMA PRIME designation, affording priority review fee waivers and rolling review eligibility in both jurisdictions. Cellectar recently closed an oversubscribed financing of up to $140 million with institutional healthcare investors to fund the confirmatory study and NDA filing, providing what appears to be sufficient runway for the regulatory programme ahead.

The phospholipid drug conjugate platform differentiates iopofosine mechanistically from both BTKi and standard chemoimmunotherapy salvage regimens, and the fixed-dosing schedule could prove attractive to patients and prescribers if the efficacy holds in a randomised setting.