Iopofosine I 131 Yields Deep Responses in R/R Waldenström Macroglobulinemia

"The results from this pivotal study utilizing just 4 doses of iopofosine monotherapy in heavily pretreated patients are very compelling, demonstrating deep and durable remissions," according to Sikander Ailawadhi, MD.

The potential first-in-class radiotherapy candidate iopofosine I 131 produced deep, enduring responses among those with relapsed/refractory Waldenström macroglobulinemia, according to a press release from Cellectar Biosciences on findings from the phase 2 CLOVER-WaM study (NCT02952508).

Treatment with iopofosine I 131 elicited a major response rate (MRR) of 61.0% (95% CI, 44.50%-75.80%; P <.0001), meeting the trial’s primary end point. Additionally, investigators reported an overall response rate (ORR) and disease control rate (DCR) of 75.6% and 100.0%, respectively. The median duration of response (DOR) was not reached, and the progression-free survival (PFS) rate was 76% after a median follow-up of 8 months. A stringent complete response (sCR) was reported in 8% of patients.

Investigators highlighted no discontinuation of the study drug due to treatment-related adverse effects (TRAEs). The most common grade 3 or higher TRAEs included thrombocytopenia (55%), neutropenia (37%), and anemia (26%). Febrile neutropenia was reported in 2% of patients. Additionally, findings highlighted no clinically significant bleeding events or deaths related to study treatment. Investigators concluded that treatment with iopofosine I 131 was well tolerated, and that the agent’s safety profile was comparable with previously reported data.

“There is a critical need for new therapies with novel mechanisms of action to treat [Waldenström macroglobulinemia],” lead study investigator Sikander Ailawadhi, MD, professor of medicine at Mayo Clinic, said in the press release. “The results from this pivotal study utilizing just 4 doses of iopofosine monotherapy in heavily pretreated patients are very compelling, demonstrating deep and durable remissions. The combination of the safety profile and deep, durable responses with a high proportion of patients remaining treatment free is impressive.”

Investigators of the single-arm, registrational CLOVER WaM study evaluated treatment with iopofosine I 131 among a target enrollment of 50 patients. As of the data cutoff of January 3, 2024, evaluable patients included those who received the study agent at more than 60 mCi and were followed up with for 60 or more days following their last dose.

The trial’s secondary end points included ORR, treatment-free survival, DOR, and clinical benefit rate.

Patients 18 years and older with histologically or cytologically confirmed Waldenström macroglobulinemia and an ECOG performance status of 0 to 2 were able to enroll on the trial. Additional eligibility criteria included having a life expectancy of 6 or months. as well as receiving prior treatment with at least 2 lines of therapy for their disease.

The modified intent-to-treat (ITT) population consisted of 45 patients with a median age of 71 years and a median IgM level of 2185 prior to beginning study treatment. Additionally, 90% of patients had refractory disease, including those who were refractory to prior treatment with a Bruton tyrosine kinase (BTK) inhibitor (50%), or anti-CD20 agents (40%). Investigators reported that 80% of the population received prior treatment with a BTK inhibitor.

“Iopofosine’s high [MRR] and achievement of the study’s primary end point in highly refractory [patients with] Waldenström macroglobulinemia exhibits its potentially practice-changing clinical profile,” James Caruso, president and chief executive officer at Cellectar, concluded. “We believe the currently impressive response rates and the [DORs] will continue to improve as the data mature. We plan to include these outcomes in our [new drug application] submission and will be requesting an accelerated approval based upon our [Waldenström macroglobulinemia] fast track designation.”

Reference

Cellectar Biosciences announces positive topline data achieving primary endpoint in pivotal clinical study of iopofosine I 131 in Waldenstrom’s macroglobulinemia. News release. Cellectar Biosciences, Inc. January 8, 2024. Accessed January 8, 2024. https://shorturl.at/gBCY9