Cellectar's iopofosine I 131 shows 87.5% ORR in post-BTKi WM subset

Cellectar Biosciences has presented a subgroup analysis from its Phase 2b CLOVER WaM trial showing that iopofosine I 131 produced an 87.5% overall response rate (ORR) in 24 patients with relapsed or refractory Waldenström macroglobulinemia (WM) who had received a BTK inhibitor (BTKi) immediately prior to treatment. The data were unveiled at the International Workshop for Waldenström Macroglobulinemia in Palm Springs, California.

The 24-patient subset represented a heavily pre-treated group: 75% were BTKi-refractory, more than 54% had received multiple BTKi regimens, and the median number of prior therapy lines was three. Notably, 17% carried TP53 mutations and 29% were MYD88 wild type, both features associated with aggressive disease and limited responsiveness to available agents. Against that backdrop, the headline figures were notable: a major response rate (MRR) of 79.2%, a clinical benefit rate (CBR) of 100%, a median duration of response of 16 months, and a treatment-free survival of 19.1 months. On safety, treatment-emergent adverse events occurred in fewer than 10% of patients, with Grade 3 or above events confined to cytopenias.

Regulatory path

Cellectar is preparing to submit a New Drug Application to the US Food and Drug Administration under the accelerated approval pathway in the first half of 2027, supported by surrogate endpoints, including MRR and duration of response, that the company says the FDA has indicated are reasonably likely to predict clinical benefit. The drug already holds Breakthrough Therapy Designation in WM, alongside six Orphan Drug and two Fast Track designations across various indications, and the European Medicines Agency has granted it PRIME designation.

In parallel, the company is moving to initiate a confirmatory Phase 3 randomised trial in a post-first-line, post-BTKi population, with site selection underway and first patient dosing expected in the first quarter of 2027. Progression-free survival will serve as the primary endpoint in that registration-directed study.

Jarrod Longcor, chief operating officer of Cellectar, said the data offer "something WM patients rarely get after BTK inhibitors: deep, durable responses from a short, fixed course of treatment," attributing the activity profile to the drug's phospholipid drug conjugate delivery mechanism, which delivers iodine-131 to cancer cells independently of the BTK pathway.

Market context

WM is a rare B-cell lymphoma affecting an estimated 1,000 to 1,500 patients newly diagnosed in the United States each year. BTKi therapy, principally ibrutinib and zanubrutinib, has become the standard of care for most patients, but a meaningful proportion eventually develop resistance or intolerance, leaving a clinically difficult post-BTKi setting with few well-validated options. Covalent BTKi resistance, often driven by mutations at the C481 binding site, has prompted interest in non-covalent BTKi agents such as pirtobrutinib, and also in regimens that bypass the BTK pathway entirely. Iopofosine I 131's targeted radiotherapy mechanism positions it as complementary rather than competitive to next-generation BTKi approaches, a distinction that may prove commercially relevant if the Phase 3 data hold. Investors will watch closely for the full CLOVER WaM dataset and any update on financing, given that a simultaneous Phase 3 initiation and NDA submission represent a capital-intensive near-term programme for a NASDAQ small-cap.