From the IWMF Torch – October 2024

The new WM-NET clinical trials network continues to play an important role in fulfilling Dr. Treon’s prediction, that a cure is in sight, with the exciting news that more centers have been added to the initial list of 15 participating institutions. The added centers are Emory University in Georgia, University of California San Diego, University of Pennsylvania, Moffitt Cancer Center in Florida, and Atrium Health Carolinas Medical Center in North Carolina. WM-NET is currently US-based but is advised by US and international WM specialists.

The impetus for WM-NET came from the Bing Center for WM at Dana-Farber Cancer Institute (DFCI), which continues to lead its development, and the network has become a reality with important five-year funding from IWMF and other donors. Clinical trials are essential to develop novel drugs and new therapy combinations that will lead us to improvements in care and to a cure. But, as Dr. Jorge Castillo of the Bing Center noted previously, “WM poses several challenges for clinical trials.” WM is a rare disease, most often diagnosed and treated within the community healthcare setting, which often provides limited access to clinical trials. On the other hand, while multiple clinical trials for WM may be open, they are competing for enrollment from a small patient population. Yet another challenge is that clinical trials for WM are often conducted at a single institution, making it difficult for would-be participants to invest in the travel, time, and financial commitments required. These and other barriers to clinical trial participation are the reasons why WM-NET was developed.

To at least partly address some of these challenges, DFCI convened a group of clinician-researchers to identify important clinical questions and design clinical trials to answer them. Also, the group’s intention is to include more trial locations to allow for faster patient enrollment and to make it easier for patients to travel and participate. There is high interest in developing trials of novel agents that are of limited duration, and it is felt that trials should include cutting-edge genomic testing, biobanking, and quality-of-life assessments. According to Dr. Castillo, the initiatives for a WM-NET database and a biobank are now under way.

At the present time, WM-NET includes three clinical trials, with two more planned. WM-NET1 is a Phase 2 study of the antibody-drug conjugate loncastuximab tesirine in WM patients who have had at least two prior treatments (including an anti-CD20 antibody such as rituximab and a BTK inhibitor such as ibrutinib or zanubrutinib). An antibody-drug conjugate is designed to deliver a toxin directly targeted to tumor cells. WM-NET2 was just added and is a Phase 2 study in previously treated WM patients of the bispecific antibody epcoritamab (see more about the epcoritamab study on page 20 of this Torch issue). WM-NET3, also called the ZEBRA trial, is a Phase 2 study of zanubrutinib + bendamustine + rituximab in treatment naïve WM that will begin enrollment in January 2025. Information about these trials can be found on www.clinicaltrials.gov.

The two planned WM-NET trials include the PROVEN study of pirtobrutinib, venetoclax, and rituximab in treatment naïve WM and the bispecific antibody ABBV-383 in previously treated WM. Stay tuned as more information about these planned trials becomes available.

To read about the concept and development of WM-NET, go to page 5 of the January 2024 Torch issue.

Map of the US with Clinical Trial sites.

U.S. Academic Cancer Centers: 20

(Matched to map—left to right)

 

• Fred Hutchinson, Seattle, WA

• Stanford University, Palo Alto, CA

• City of Hope, Duarte, CA

• University of California, San Diego, La Jolla, CA

• Huntsman Cancer Center, SLC, UT

• Colorado Blood Cancer Institute, Denver, CO

• Mayo Clinic, Rochester, MN

• Northwestern University, Chicago, IL

• UT Southwestern Medical Center, Dallas, TX

• FLMD Anderson, Houston, TX

• Cleveland Clinic, Cleveland, OH

• Ohio State University, Columbus, OH

• Memorial Sloan Kettering Cancer Center, NY, NY

• Dana Farber Cancer Institute, Boston, MA

• University of North Carolina, Chapel Hill, NC

• Mass General Hospital, Boston, MA

• Beth Israel Deaconess Medical Center, Boston, MA

• Emory University, Atlanta, GA

• Moffitt Cancer Center, Tampa, FL

• University of Miami, Miami, FL