CLOVER WaM Trial of Iopofosine I 131 Meets Primary End Point in WM

Iopofosine I-131 showed impressive results in a study for patients with advanced Waldenstrom's macroglobulinemia, achieving a major response rate of 61%.

Blood Cancer: © Hadi - stock.adobe.com XPENG

CLOVER WaM Trial of Iopofosine I 131 Meets Primary End Point in WM

The CLOVER WaM trial (NCT02952508) evaluating treatment with iopofosine I 131 for patients with relapsed/refractory Waldenstrom’s macroglobulinemia (WM) that have received at least 2 prior lines of therapy, including Bruton tyrosine kinase inhibitors (BTKi) met its primary end point with a major response rate (MRR) of 61% (95% CI, 44.50%-75.80%; 2-sided P <.0001).1

Responses observed in the study were durable with an overall response rate of 75.6% in evaluable patients. All patients experienced disease control, the median duration of response was not reached, and at a median follow-up of 8 months, 76% of patients remained progression-free.

Further, these outcomes exceed real world data, which demonstrate a 4-12% MRR and a duration of response of approximately 6 months or less despite continuous treatment in a patient population that is less pretreated and less refractory to multiple classes of drugs. Notably, iopofosine monotherapy achieved an 8% stringent complete remission in this highly refractory WM population.

"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 6 months,” Sikander Ailawadhi, MD, professor of medicine at Mayo Clinic, and lead investigator in the CLOVER WaM study, said in a press release. “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."

Iopofosine I 131 is a potential first-in-class, targeted radiotherapy candidate. Previously reported data has shown the agent to be well tolerated. Iopofosine I 131 is being evaluated in CLOVER WaM, the largest study to date in patients with relapsed or refractory WM post-BTKi therapy.

The single-arm CLOVER WaM trial is fully enrolled. Patients were required to have histologically or cytologically confirmed WM, an ECOG performance status of 0 to 2, a life expectancy of at least 6 months, and have received at least 2 prior lines of therapy for WM.2

With a data cut-off date of January 3, 2024, topline safety data is being reported on 45 patients who meet criteria for modified intent to treat (mITT).1 The 41 patients in the efficacy evaluable population must have received a total administered dose of greater than 60 mCi and had follow-up of at least 60 days following treatment with their last dose.

The median age of the mITT patients was 71 years. The median IgM level prior to treatment with iopofosine was 2,185, and 90% of patients were refractory to either a BTKi (50%) or anti-CD20 therapy (40%). Further, 26.7% of patients were multiclass refractory, and 80% were previously treated with a BTKi.

Iopofosine I 131 had a toxicity profile consistent with previously reported safety data, and no treatment-related adverse events (TRAEs) led to discontinuation of treatment. Grade 3 or greater TRAEs which were seen in more than 10% of patients included thrombocytopenia (55%), neutropenia (37%), and anemia (26%). All patients recovered from cytopenias with no reported aplastic sequelae, there were no clinically significant bleeding events, and the rate of febrile neutropenia was 2%. Further, no treatment-related deaths were reported.

Recent Approvals Signal a Bright Future for Myelodysplastic Syndromes

New treatments, including luspatercept-aamt, have been added to the treatment algorithm of patients with low-risk myelodysplastic syndrome in 2020.

Axatilimab Presents a New Treatment Horizon for Chronic GVHD

In an interview with Targeted Oncology, Daniel Wolff, MD, discussed findings from the phase 2 AGAVE-201 trial evaluating axatilimab as a potential treatment option for patients with chronic graft-vs-host disease.

BGB-16673 Shows Responses With a Manageable Safety Profile Across R/R B-Cell Malignancies

The novel BTK degrader BGB-16673 was well tolerated; produced meaningful and rapid clinical responses; and demonstrated on-target effects in patients with relapsed/refractory B-cell malignancies.

Orca-Q Demonstrates Early Efficacy, Tolerable Safety in Haploidentical Stem Cell Transplant Without PTCy

The high-precision cellular product Orca-Q demonstrated early signals of clinical activity as well as an acceptable safety profile for patients undergoing haploidentical stem cell transplantation without posttransplant cyclophosphamide.

Zanubrutinib Shows Viability After Intolerance to Acalabrutinib in B-Cell Malignancies

Results from an ongoing phase 2 study show the viability for the use of zanubrutinib after patients with previously treated B-cell malignancies are deemed intolerant to the next-generation Bruton tyrosine kinase inhibitor acalabrutinib.

Iptacopan Deliveres Hematological Benefits in PNH/Persistent Anemia

Data from the phase 3 APPLY-PNH trial show comprehensive control of intravascular and extravascular hemolysis with iptacopan in patients with paroxysmal nocturnal hemoglobinuria and persistent anemia.