On April 26, 2022 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a late-stage clinical biopharmaceutical company focused on the discovery, development and commercialization of targeted drugs for the treatment of cancer, reported an independent Data Monitoring Committee (DMC) has completed its planned futility/efficacy assessment of the company’s pivotal Phase 2b study of iopofosine in Waldenstrom’s macroglobulinemia (WM) and unanimously recommended continuation of the trial as planned (Press release, Cellectar Biosciences, APR 26, 2022, View Source [SID1234612961]).
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"We remain highly encouraged with the consistent performance of iopofosine I-131 in this difficult-to-treat refractory patient population," said James Caruso, president and chief executive officer of Cellectar. "We have alignment with the FDA on a 20% major response rate hurdle as the primary endpoint of our pivotal study. In a poster presented at ASCO (Free ASCO Whitepaper) 2021, we showed an 83.3% major response rate with one complete response in six WM patients, which served as the basis for our pursuing this indication."
The pivotal trial is a global, non-comparator, single-arm, open-label expansion cohort of the currently ongoing Phase 2 CLOVER-1 study of CLR 131. The study will enroll 50 WM patients. Patients in the trial will receive up to four doses of iopofosine over two cycles (cycle one on days 1, 15, and cycle two on days 57 and 71). The primary endpoint of the trial is major response rate as defined as a partial response (a minimum of a 50% reduction in the biological marker IgM) or better in patients that receive a minimum total body dose of 60 mCi with secondary endpoints of treatment free survival, duration of response and progression free survival.
The DMC is an independent committee of clinical research experts who review data in ongoing clinical trials. The DMC assessment was based on a pre-specified futility analysis within the first 10 patients as defined in the study protocol.
About Waldenstrom’s macroglobulinemia
Waldenstrom’s macroglobulinemia (WM) is a rare and incurable disease defined by specific genotypic subtypes that defines patient responses and long-term outcomes. The U.S. annual incidence is 3,000 (anticipated annual growth rate of approximately 30% through 2025) with a current U.S. prevalence of approximately 45,000 patients. The U.S. represents approximately 43% of the global market. WM is a lymphoma, or cancer of the lymphatic system. The disease occurs in a type of white blood cell called a B-lymphocyte or B-cell, which normally matures into a plasma cell whose job is to manufacture immunoglobulins (antibodies) to help the body fight infection. In WM, there is a malignant change to the B-cell in the late stages of maturing, and it continues to proliferate into a clone of identical cells, primarily in the bone marrow but also in the lymph nodes and other tissues and organs of the lymphatic system. These clonal cells over-produce an antibody of a specific class called IgM.
WM cells have characteristics of both cancerous B-lymphocytes (NHL) and plasma cells (multiple myeloma), and they are called lymphoplasmacytic cells. For that reason, WM is classified as a type of non-Hodgkin’s lymphoma called lymphoplasmacytic lymphoma (LPL). About 95% of LPL cases are WM; the remaining 5% do not secrete IgM and consequently are not classified as WM.
There is no standard treatment for WM. Several drugs have demonstrated activity either alone or in combinations, but only a single drug has received regulatory approval. Treatment is mainly focused on the control of symptoms and the prevention of organ damage. Front-line treatments for WM include rituximab alone or in combination with other agents. In the salvage therapy (second line or later) setting, ibrutinib, combinations of proteosome inhibitors and immunomodulatory drugs and stem cell transplantation are considered. Ibrutinib is the only drug to receive regulatory approval (2015) as a salvage therapy; in late 2019, it was approved for front-line treatment in combination with rituximab. Factors such as long-term cytopenias, age, hyper viscosity, the need for quick disease control, lymphadenopathy, co-morbidities, and IgM-related end-organ damage are key considerations in the choice of treatment.