Cellectar reports an 87.5% response rate and 79.2% major response rate with iopofosine I 131 after BTK inhibitors in Waldenström macroglobulinemia.
Written By: Charvi Kalal, PharmD
Reviewed By: Pharmacally Editorial Team
Cellectar Biosciences announced on October 15, 2026, efficacy results from a subgroup of patients in its Phase 2b CLOVER WaM trial who received iopofosine I 131 immediately after Bruton tyrosine kinase inhibitor (BTKi) therapy for relapsed or refractory (r/r) Waldenström macroglobulinemia (WM). The findings were presented at the International Workshop for Waldenström Macroglobulinemia, held October 14–16 in Palm Springs, California.
Treatment After BTK Inhibitor Failure
Waldenström macroglobulinemia is a rare B-cell malignancy for which BTK inhibitors are an established targeted treatment option. Patients whose disease progresses during BTKi therapy or who become refractory to treatment can face substantial therapeutic challenges, creating a need for alternative approaches.
Iopofosine I 131 is a phospholipid drug conjugate (PDC) designed to deliver iodine-131, a radioactive isotope, to cancer cells. Its radiation-based approach acts independently of the BTK pathway, providing a rationale for investigating its activity following BTKi failure. The US Food and Drug Administration (FDA) has granted the investigational therapy several designations across cancer indications, including Breakthrough Therapy and Fast Track designations. The European Medicines Agency has also granted it PRIME designation.
Study Design and Patient Characteristics
The analysis included 24 patients from the Phase 2b CLOVER WaM trial who received iopofosine I 131 immediately after BTKi therapy. The results were derived from a previously reported 12-month follow-up dataset.
The population had substantial prior treatment exposure. Approximately 75% of patients were refractory to BTKi therapy, while more than 54% had received multiple BTK inhibitors. Patients had received a median of three previous lines of therapy, with a range of two to seven. TP53 mutations were present in 17% of patients, while 29% had wild-type MYD88, features the company associates with more challenging disease characteristics.
The regimen used two treatment cycles, with iopofosine I 131 administered at 15 mCi/m² on days 1 and 15 of each 57-day cycle.
Response Rates and Durability
The subgroup achieved an overall response rate (ORR) of 87.5% and a major response rate (MRR) of 79.2%. The clinical benefit rate was 100%. Median duration of response (DoR) was 16 months, while median treatment-free survival was 19.1 months.
The response rates indicate substantial observed antitumour activity in this selected post-BTKi population. The median DoR also suggests that responses were not limited to short-term disease control. However, the reported treatment-free survival requires careful interpretation because the announcement does not provide its calculation method or a comparator against which to assess the result.
Cellectar reported treatment-emergent adverse events in fewer than 10% of patients, with cytopenias the only grade 3 or higher events. The company considers the efficacy and follow-up data relevant to its proposed accelerated-approval strategy, particularly the major response rate and duration of response. The available summary, however, does not provide sufficient detail to independently assess the complete safety profile.
Phase 3 Development and Regulatory Plans
Cellectar is preparing a randomized Phase 3 confirmatory trial in patients previously treated with first-line therapy and BTK inhibitors. The study is expected to use progression-free survival as its primary endpoint, with the first patients anticipated to be dosed in the first quarter of 2027.
The company also plans to submit a New Drug Application to the FDA seeking accelerated approval in the first half of 2027. These remain company projections and are not evidence that the FDA has accepted the proposed regulatory pathway or determined that the available data are sufficient for approval.
Clinical Interpretation
The combination of an 87.5% ORR, a 79.2% MRR and a 16-month median DoR provides an encouraging efficacy signal in a heavily pretreated population following BTKi therapy. A finite treatment course could offer practical advantages over continuous treatment, although the study does not establish comparative benefits in treatment burden, quality of life or clinical outcomes.
The findings nevertheless remain preliminary. They come from only 24 patients in a subgroup of a single-arm Phase 2b study, without a comparator or confidence intervals in the reported summary. The results do not establish a progression-free or overall survival benefit, and the limited safety reporting warrants further assessment, particularly regarding hematologic toxicity and longer-term effects.
The planned randomized Phase 3 study will be important in determining whether the observed responses translate into clinically meaningful benefit. Until more complete data become available, iopofosine I 131 should be viewed as an investigational treatment with promising response results rather than an established alternative to existing post-BTKi therapies.
Reference
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, Cellectar Biosciences, October 15, 2026
Study of Iopofosine I-131 (CLR 131) in Select B-Cell Malignancies (CLOVER-1) With Expansion in Waldenstrom (CLOVER-WaM), ClinicalTrials.gov ID NCT02952508
About the Writer
Charvi Kalal (LinkedIn) is a Pharm.D intern and aspiring medical writer with hands-on experience in medical writing, clinical research, pharmacovigilance, and clinical pharmacy. She has experience in medical content writing through CliMed, along with exposure to ADR monitoring, prescription analysis, patient counselling, literature review, and research documentation. Her research focuses on ADR monitoring and reporting in breast cancer patients receiving targeted therapy. With certifications in GCP, biomedical research, scientific writing, and clinical research, she is passionate about transforming scientific evidence into accurate, engaging, and accessible healthcare content