Project Term
–
Project Summary
I focus on developing bispecific antibodies (BsAb) for the treatment of B-cell non-Hodgkin lymphoma (B-NHL). We are testing chemo-free epcoritamab or mosunetuzumab combinations in follicular lymphoma, incorporating glofitamab or epcoritamab in the treatment of aggressive lymphomas, studying resistance mechanisms in patient samples from our trials, analyzing our experience to increase BsAb safety. Our goal is to leverage BsAb to improve upon current standards and shift B-NHL treatment paradigms.
Lay Abstract
Non-Hodgkin lymphoma (NHL) is among the most common cancers and causes of cancer-related death worldwide. Follicular lymphoma (FL) and diffuse large B cell lymphoma (DLBCL) are the most frequent types of NHL. While often curable or treatable, NHL is still lethal for far too many patients and novel, lifesaving therapies are needed.
My research aims to improve outcomes of individuals affected by NHL by using a novel immunotherapy called bispecific antibodies (BsAb). These drugs physically bring together lymphoma cells and the patient’s immune cells, enabling the latter to recognize the lymphoma cells and destroy them. There are 3 main BsAb: mosunetuzumab, epcoritamab, and glofitamab. I have been involved with BsAb research since its beginning and am leading key clinical trials in this field.
In patients with FL that came back after chemotherapy we are testing the combination of epcoritamab, rituximab, and lenalidomide (the latter two being an approved therapy), while in those with newly diagnosed FL we explore mosunetuzumab, with or without zanubrutinib (another approved drug). Our preliminary results show that chemo-free treatments are safe and highly effective. In patients with recurrent DLBCL we explored glofitamab alone or combined with RO7443904, a "booster" BsAb, while in individuals with newly diagnosed high-risk DLBCL, we are leading two studies where we add glofitamab or epcoritamab to standard chemotherapy to improve its results. We are also working in the lab to better understand how BsAb work and why, sometimes, they don’t. We want to use this knowledge to plan our next trials. Finally, we have established a database of all our patients treated with BsAb to be able to examine our experience, learn from it, and identify gaps in knowledge that can help make this treatment safer and better.
The overarching idea of our program is that BsAb may either replace (in the case of FL) or enhance (in DLBCL) standard treatments. Large studies to definitively test these ideas have begun, which tells us that our research is headed in the right direction.
Program
Grant Subprogram
