Cellectar Biosciences (CLRB) Study Update summary

Study design and patient population

• CLOVER-WaM is a global, open-label, single-arm pivotal study of iopofosine I-131 in relapsed/refractory Waldenstrom's macroglobulinemia (WM) patients, including those with CNS involvement, who had received at least two prior therapies, including BTKi.

• 65 patients enrolled; 55 met criteria for the modified intent-to-treat (MITT) efficacy population, with a median age of 70 and a median of 4 prior therapies.

• 71% had prior BTK inhibitor, 91% prior rituximab, and 84% prior multi-agent chemotherapy; 40% were dual-class refractory, 27% triple-class refractory, and 27% refractory to all available therapies.

• Over half were medium/high risk by IPSSWM, and ~30% had MYD88 wild-type, a marker of BTK inhibitor resistance.

Efficacy results

• Achieved primary endpoint: 56.4% major response rate (partial response or better), with lower bound of 42%, and 80% overall response rate, surpassing the FDA-agreed threshold.

• 98% disease control rate observed, with durable responses across all subgroups, including high-risk and refractory patients.

• 7.3% complete or very good partial response, including in high-risk and refractory subgroups.

• Major responses were durable, with median duration not reached at 9.7 months median follow-up; 18-month duration of response projected at 72–78%.

• 78% of major response patients and 72% of all responders remained progression-free at 18 months.

Safety and tolerability

• Iopofosine I-131 was well tolerated; main grade 3+ adverse events were thrombocytopenia (80%), neutropenia (69.2%), anemia (44.6%), lymphopenia (13%), and infections (12.3%).

• Cytopenias were predictable, manageable, and resolved in all patients; only one AE-related death (infection), no significant off-target toxicities.

• No treatment-induced peripheral neuropathy, cardiotoxicity, hepatic toxicity, renal toxicity, or significant bleeding.

• Most common adverse events were hematologic, which were predictable, manageable, and resolved within weeks.