Dual-Antibody Targeted Therapy Being Tested Against Follicular Lymphoma

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Follicular lymphoma (FL) is the second-most common lymphoid malignancy in the United States, and while many people initially respond to treatment, they almost always relapse. As a result, patients often require numerous treatments during their lifetime.

Juan Pablo Alderuccio
Juan Pablo Alderuccio, M.D.

To test an innovative approach against FL, researchers at Sylvester Comprehensive Cancer Center at the University of Miami’s Miller School of Medicine are conducting a phase 2 clinical trial using a dual-antibody targeted therapy(ClinicalTrials.gov NCT04998669).

“Patients with asymptomatic relapsed or refractory FL do not necessarily require immediate treatment,” said Juan P. Alderuccio, M.D., assistant professor of clinical medicine in the Division of Hematology and principal investigator of the study. “However, patients experiencing early treatment failure, defined by lymphoma progression within 24 months (POD24) of diagnosis, represent a high-risk group associated with shorter survival. In patients exhibiting POD24 or significant tumor burden, immediate treatment is indicated.

“In this trial, we will test two agents — rituximab and loncastuximab tesirine — in patients with relapsed/refractory FL presenting POD24, requiring treatment initiation based on immediate need or second relapse,” he explained. “The study duration will be 10 months, and no further treatment will be pursued in patients responding to this approach.”

Rituximab, which targets the CD20 protein commonly expressed in B-cell non-Hodgkin lymphomas, has been a mainstay FL treatment for decades. Loncastuximab is a novel antibody-drug conjugate composed of a humanized anti-CD19 conjugated to a cytotoxic dimer. After binding to the tumor cells, the antibody is internalized, the cytotoxic drug is released, killing the cancer cells. CD19 is ubiquitously expressed in FL, making it an excellent target.

The researchers hope loncastuximab will be the secret sauce that gives FL patients durable responses. They are encouraged by a previous phase 1 study in which loncastuximab demonstrated substantial single-agent antitumor activity in 14 patients with relapsed/refractory FL. Of those, nine experienced complete responses, while two achieved partial responses.

Preclinical studies have demonstrated synergistic activity between rituximab and loncastuximab, further supporting the combination’s potential.

“Based on preclinical studies and data from the phase 1 trial, we think combining these two agents may significantly enhance antitumor activity,” said Dr. Alderuccio. “Positive results will inform the design of a larger, randomized, multicenter clinical trial.”

The researchers plan to enroll 39 patients and are currently recruiting. Their primary goal is to assess the complete response rate by PET/CT after 12 weeks of treatment. Secondary goals are to identify overall response rates, safety and tolerability, and progression-free survival at two years. Researchers will also test imaging biomarkers that incorporate artificial intelligence.

“Currently, no single standard of care exists for patients with relapsed/refractory FL,” said Dr Alderuccio. “Approved agents have clinical activity but do not offer long-term remission, and ultimately, all patients relapse. We hope this ambulatory target therapy will generate better response rates and long-term remissions.”

For more information about this phase 2 study for people with relapsed or refractory follicular lymphoma, please contact Dr. Alderuccio at jalderuccio@med.miami.edu.

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