Iopofosine I-131 (CLR 131) has shown significant efficacy in patients with relapsed or refractory Waldenström macroglobulinemia (WM), according to results from the phase 2 CLOVER-WaM trial. The study met its primary endpoint, demonstrating a major response rate (MRR) of 56.4% (95% CI, 42%-67%) in patients who had received at least two prior lines of therapy. These findings suggest that iopofosine I-131 could offer a valuable new treatment option for this challenging patient population.
The observed MRR significantly exceeded the prespecified endpoint of 20%. Furthermore, the modified intention-to-treat (mITT) population (n = 55) achieved an overall response rate (ORR) of 80% and a disease control rate of 98.2%. These results are particularly noteworthy given that approximately 27% of patients were refractory to all available therapies, including BTK inhibitors, anti-CD20 antibodies, and chemotherapy, and 40% were dual-class refractory to a BTK inhibitor and rituximab.
Durability of Response
In patients who achieved a major response or overall response, the median duration of response (DOR) was not yet reached at the time of data cutoff. The 18-month progression-free survival rates were 78% for patients experiencing a major response and 72% for those achieving an overall response, indicating a sustained clinical benefit.
Subgroup Analysis
Additional data revealed consistent responses across various patient subgroups, including those with MYD88 wild-type disease (ORR 81%, n = 16), P53-mutated disease (ORR 80%, n = 5), and those treated after a BTK inhibitor (ORR 72%, n = 39). Patients with dual-class refractory disease showed an ORR of 59% (n = 22), while those with triple-class refractory disease had an ORR of 53% (n = 15).
Safety Profile
The safety data were consistent with previously reported findings for iopofosine I-131. Notably, no cardiovascular, renal, or liver toxicities were reported, and no patients experienced peripheral neuropathy or significant bleeding. The most common treatment-emergent adverse effects were hematologic, including thrombocytopenia, neutropenia, and anemia, which were generally manageable.
Regulatory Plans
"The outcomes observed in this study continue to far exceed expectations and provide evidence of the potential for iopofosine in a broad range of patients with Waldenström macroglobulinemia, including difficult-to-treat subgroups," said James Caruso, president and CEO of Cellectar Biosciences. "We believe with these results that iopofosine I-131 has the potential to become the standard-of-care therapy for relapsed/refractory patients."
Cellectar Biosciences plans to submit a new drug application (NDA) to the FDA in the fourth quarter of 2024 and will be seeking priority review, which provides an estimated 6-month regulatory review period.
About Iopofosine I-131
Iopofosine I-131 is a small-molecule phospholipid drug conjugate designed to deliver the radioisotope iodine-131 directly to cancer cells. It is currently under investigation and has not been approved for use in any country for any indication.
CLOVER-WaM Trial Details
The CLOVER-WaM trial was an expansion cohort of the open-label, multicenter CLOVER-1 trial, enrolling patients with relapsed/refractory B-cell malignancies. Patients enrolled in the CLOVER-WaM cohort had histologically or cytologically confirmed Waldenström macroglobulinemia and had received at least two prior lines of therapy. Key inclusion criteria included an ECOG performance status of 0 to 2, a life expectancy of at least 6 months, and measurable immunoglobulin M (IgM) above the upper limit of normal, along with measurable nodal and extranodal lesions.
