Iopofosine I 131 produced strong responses in Waldenström macroglobulinemia, according to 12-month folllow-up data from CLOVER WaM requested by the FDA.
The phospholipid-drug conjugate radiotherapeutic Iopofosine I 131 (CLR 131) exhibited strong efficacy data, including durable responses, in patients with relapsed or refractory Waldenström macroglobulinemia, according to a report of long-term follow-up data from the phase 2b CLOVER WaM trial (NCT02952508) that was requested by the FDA .1
Data showed that patients in the per-protocol population (n =55) achieved a major response rate (MRR) of 61.8% and an overall response rate (ORR) of 83.6%. Patients also experienced a median duration of response (DOR) of 17.8 months in addition to a 13.5-month median progression-free survival (PFS). These data met both primary and secondary end points for the trial and support the filing of an NDA seeking accelerated approval from the FDA. Notably, the FDA also granted
Moreover, in patients with Waldenström macroglobulinemia who had either received prior BTK inhibition (n = 39) or were refractory to BTK inhibitors (n = 33), the respective MRRs were 64.1% and 63.6%. The median DOR was 18.2 months in both subgroups, and the median PFS values were 15.9 months and 14.8 months, respectively.
“The depth, durability, and consistency of responses observed across both the total population and BTK inhibitor–treated subsets underscore iopofosine I 131’s potential as a meaningful new treatment option in Waldenström macroglobulinemia and differentiate it from currently available therapies,” Jarrod Longcor, chief operating officer of Cellectar Biosciences, stated in a news release. “With the completion of at least 12-month follow-up on all patients, we believe this dataset meets key regulatory expectations for an accelerated approval submission and positions us well as we advance toward initiating our confirmatory study.”
The open-label, multicenter trial enrolled patients who were at least 18 years of age with histologically or cytologically confirmed Waldenström macroglobulinemia.3 Patients also needed to have an ECOG performance status of 2 or lower, a life expectancy higher than 6 months, and received at least 2 prior lines of therapy for Waldenström macroglobulinemia.
If patients had ongoing grade 2 or higher adverse effects (AEs) from prior treatments, malignancies in addition to Waldenström macroglobulinemia, or received total- or hemi-body irradiation prior to enrollment, they were not included in the trial.
Iopofosine I 131 in Waldenström macroglobulinemia: CLOVER-WaM Highlights
Patients received a fixed-dose regimen of 4 approximately 30-minute infusions of iopofosine I 131.1
MRR served as the trial’s primary end point, whereas DOR, ORR, and clinical benefit rate served as as secondary end points.1,2
Baseline characteristics revealed that patients had received a median of 4 prior lines of therapy (range, 2-15).1 Among patients who had received prior BTK inhibition, 77% had refractory disease compared with 60% of those who had received prior chemotherapy and 58% of those who were previously exposed to both BTK inhibitors and rituximab (Rituxan).
Patients in the per-protocol population achieved a very good partial response or complete response rate of 14.5% and a disease control rate of 98.2%.
Regarding safety, iopofosine I 131 demonstrated a predictable and manageable safety profile, with rates of bleeding AEs and infections both occurring in less than 10% of patients. Cytopenias were reported as the most common treatment-emergent AEs, and the nonhematologic AEs were primarily grade 2 or less.
“These mature 12-month follow-up data, as required by the FDA, further strengthen the compelling clinical profile of iopofosine I 131,” James Caruso, president and chief executive officer of Cellectar Biosciences, concluded in the news release. “Importantly, the durability of response continues to improve over time, and the consistency of activity in post–BTK inhibitor patients reinforces the potential of iopofosine I 131 to address a critical unmet need in the second-line setting and beyond. We remain committed to providing iopofosine I 131 to the thousands of patients who can benefit from treatment and plan to initiate our confirmatory study.”
