CLOVER WaM trial: Iopofosine I 131 exceeds primary endpoint of major response rate in patients with Waldenstrom’s macroglobulinemia

Iopofosine I 131 (I-131) is an investigational, first-in-class, targeted radiotherapeutic candidate for the treatment of patients with relapsed/refractory (R/R) Waldenstrom’s macroglobulinemia (WM). I‑131 previously met the primary endpoint in the pivotal CLOVER-WaM (NCT02952508) trial in patients with WM who had received ≥2 therapies including Bruton’s tyrosine kinase (BTK) inhibitor.

On July 23, 2024, it was announced that I-131 exceeded the primary endpoint of major response rate (MRR) in the CLOVER-WaM trial.

Topline efficacy data in evaluable patients (n = 55) at data cut-off were as follows:

• Overall response rate (ORR) achieved in 80% of patients.
• MRR achieved in 56.4% (95% CI, 0.42–0.67) of patients, which exceeded the agreed primary endpoint of a 20% MRR.
• Disease control rate achieved in 98.2% of patients.
• Median duration of response in patients achieving MRR and ORR were not reached, with 78% and 72% of patients, respectively, remaining free from disease progression at 18 months.
• Responses were shown in difficult-to-treat, high-needs patient populations:
  • Median number of prior lines of therapy was 4.
  • Approximately 27% of patients were refractory to all available therapies, and 40% were dual-class refractory (BTK inhibitor and rituximab).
• ORRs was comparable across clinically challenging disease subgroups, including: MYD88-wt (81%; n = 16), P53-mutated (80%; n = 5), and clinical patient cohorts including post-BTK inhibitor (72%; n = 39), as well as dual-class (59%; n = 22), and triple-class (53%; n = 15) refractory patients.

I-131 was previously selected by the European Medicines Agency (EMA) for Priority Medicines (PRIME) designation in patients with WM with ≥2 prior treatment regimens.

‘The International Waldenstrom’s Macroglobulinemia Foundation (IWMF) and the Lymphoma Hub are working in collaboration for patients with Waldenstrom’s macroglobulinemia. This initiative aims to increase awareness of Waldenstrom's macroglobulinemia among healthcare professionals, patients, caregivers, and the patient advocacy community. 

This initiative is funded by Cellectar Biosciences. All content is developed independently by SES in collaboration with an expert steering committee; funders are allowed no direct influence on the content of the hub.’