Novel Drug Shows 100% Disease Control Rate in WM

The novel agent, iopofosine I 131, is showing promise for the treatment of patients with relapsed or refractory Waldenstrom’s macroglobulinemia (WM), according to topline findings from the CLOVER WaM study, which were announced in a press release from Cellectar Biosciences, the manufacturer of the drug.

According to the American Cancer Society, WM is a subtype of non-Hodgkin lymphoma where the cancer cells produce a large amount of macroglobulin, which is an abnormal protein. The disease can be treated with plasma exchange, chemotherapy, immunotherapy, targeted therapy, radiation therapy or stem cell transplant.

The CLOVER WaM trial is investigating iopofosine I 131 in 50 patients with WM who underwent at least two prior lines of therapy, including a BTK inhibitor. Now, this data is being released for an efficacy evaluable population of 41 patients who received a total dose of 60 mCi 60 or more days ago.

“WM patients need new, clinically meaningful treatment modalities and currently, there are limited options for patients who have received prior BTK (inhibitor) therapy. Iopofosine’s product profile is notable because of its novel mechanism of action, fixed four-dose course of treatment completed within 75 days and the promise of an enhanced quality of life for patients, including a prolonged treatment-free interval,” Newton Guerin, International Waldenstrom’s Macroglobulinemia Foundation (IWMF) president and CEO, said in the press release.

Among the evaluable patient population, the median age was 71, median IgM level (a protein found in the blood used to diagnose and track the progression of WM) before treatment with iopofosine was 2,185, 90% were refractory to either a BTKi (18/36 50%) or anti-CD20 therapy (18/41 40%), with 26.7% multiclass refractory, and 80% of patients were previously treated with a BTK inhibitor.

“There is a critical need for new therapies with novel mechanisms of action to treat WM. There are no approved treatments for patients post BTKi therapy, where currently the expected response rate to salvage treatments is approximately 10%, and the expected duration of response in those patients is less than six months,” Dr. Sikander Ailawadhi, professor of medicine at Mayo Clinic, and lead investigator in the CLOVER WaM study, said in the press release.

CLOVER WaM met its main goal of major response rate (which is the percentage of patients who experience a significant reduction in serum IgM levels, symptoms and other disease markers) of 61%.

Overall response rate (percentage of patients whose cancer shrunk or disappeared from treatment) in evaluable patients was 75.6%, with 100% of patients experiencing disease control. At an average follow-up of eight months, 76% of patients did not experience disease progression.

Of note, a total of 8% of patients experienced a stringent complete remission (disappearance of cancer).

“The results from this pivotal study utilizing just four 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,” Ailawadhi said.

According to the release, the outcomes observed with iopofosine I 131 are better than what is typically observed for this patient population. Real-world data estimate that the major response rate is 4% to 12%, with a duration of response of approximately six months or shorter.

In the CLOVER WaM trial, there were no treatment-related side effects that led to patients stopping treatment. Moderate to severe (grade 3 or higher) side effects that were observed in more than 10% of patients included thrombocytopenia (55%), neutropenia (37%) and anemia (26%).

“Iopofosine’s high major response rate and achievement of the study’s primary endpoint in highly refractory, Waldenstrom’s macroglobulinemia patients exhibits its potentially practice-changing clinical profile. We believe the currently impressive response rates and the duration of responses will continue to improve as the data matures. We plan to include these outcomes in our NDA submission and will be requesting an accelerated approval based upon our WM Fast Track Designation,” James Caruso, president and CEO of Cellectar said in the release.

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