Two trials evaluate new approaches to treating non-Hodgkin and follicular lymphomas
In the past decade, immunotherapies have emerged as the fifth pillar in standard-of-care treatments for many patients with cancer. Despite the significant improvements in outcomes across many cancer types after immunotherapy, not every patient benefits.
Basic research has shown there are many ways to boost immune responses against cancer. Our institute is focused on investigating cutting-edge agents that have the potential to improve cancer outcomes. A new phase I trial open at Earle A. Chiles Research Institute, a division of Providence Cancer Institute of Oregon, is enrolling patients with advanced or metastatic solid tumors or non-Hodgkin lymphoma. This study will evaluate the safety, efficacy and side effects of WTX-330, a conditionally activated interleukin-12, when given as a single therapy.
Why the study is important
The immune system makes more than three dozen interleukins, also referred to as cytokines, which are immune proteins that regulate and enhance immune response. Interleukin-12 (IL-12) has powerful anti-tumor effects in murine models of cancer and is a leading candidate for a new generation of immunotherapies.
Previous clinical and basic research demonstrated IL-12’s antitumor activity and ability to induce immunological memory – the immune system’s adeptness in responding rapidly and effectively to pathogens already encountered. In early clinical studies, recombinant human IL-12 (rhIL-12) showed clinical activity in several tumor types including non-Hodgkin lymphoma. However, rhIL-12 also demonstrated toxicity that limited its usefulness.
WTX-330 was developed in response to the shortcomings of rhIL-12 while still maintaining anti-tumor activity. WTX-330 is a prodrug, activated in the tumor microenvironment before releasing the fully active IL-12 cytokine. The hypothesis is that WTX-330 will reduce toxicity while also enhancing antitumor activity in the tumor, thus improving benefit while minimizing harsh side effects.
The study includes both dose escalation (Part 1) and dose expansion (Part 2), with two arms (A and B). Both parts and arms of the study have distinct patient criteria. Learn about patient eligibility and more details about the study here:
Providence is the only site on the West Coast offering the WTX-330 study to patients. The principal investigator is Brendan Curti, M.D., Robert W. Franz Endowed Chair for Clinical Research and medical director of the Melanoma Program, Cytokine and Adoptive Immunotherapy and Genitourinary Oncology Research at Providence Cancer Institute.
Study will help identify high-risk patients with follicular lymphoma
Follicular lymphoma is a type of B-cell non-Hodgkin lymphoma that tends to grow slowly and can appear in the lymph nodes, bone marrow or other organs. Although there are treatments, they are largely focused on disease management. It is not uncommon for the cancer to come back.
Most patients with follicular lymphoma (FL) have an overall survival of nearly two decades. However, across randomized studies, 20% of patients will respond poorly to first line chemoimmunotherapy and account for a significant portion of early deaths in the larger population of people with FL.
A study currently open at Earle A. Chiles Research Institute is enrolling patients with grade I-IIIa follicular lymphoma that has relapsed quickly or is resistant to treatment. Currently, identifying these patients at diagnosis or prior to therapy is not possible.
Patients with FL need alternative therapies
The study’s predictive approach will help identify high-risk patients prior to any therapy, and test whether adding a targeted therapy to first line treatment can provide longer remissions, eliminate residual disease and improve outcomes for this group of patients.
Obinutuzumab targets and attaches to a protein found on B cells. Immunotherapy with obinutuzumab may induce changes in the body's immune system and may interfere with the ability of tumor cells to grow and spread.
Lenalidomide may stimulate or suppress the immune system and stop cancer cells from growing. Prior studies with lenalidomide demonstrated promising activity in treating patients with FL.
Chemotherapy agents, such as cyclophosphamide, doxorubicin, vincristine, prednisone and bendamustine, work in different ways to stop the growth of cancer cells. They either work by killing the cancer cells, by stopping them from dividing, or by stopping them from spreading.
The first arm of the study will identify promising treatment approaches, while the second arm is designed to enable identification of the high-risk group prior to therapy. Tumor biopsies and biopsy specimens from patients are required prior to enrollment.
This study is currently enrolling patients at multiple Providence sites in Oregon. The principal investigator is Charles W. Drescher, M.D., Providence Swedish Cancer Institute Gynecologic Oncology and Pelvic Surgery.
Learn more about the study here:
How to refer a patient
To refer a patient to one of these clinical trials:
New research studies are added frequently.
Providence Hematologic Malignancies Program cares for patients with cancers of the blood, bone marrow and lymph nodes, including Hodgkin and non-Hodgkin lymphomas, leukemia, myeloma and the myelodysplastic syndromes. We are among the few centers in the region capable of offering adoptive cellular therapies such as chimeric antigen receptor (CAR) T-cell therapy and tumor infiltrating lymphocytes. Patients have access to expert care from our hematology and oncology specialists, oncology nurses, radiation oncologists, pathologists, genetic-risk experts and more, as well as breakthrough research and clinical trials through the Earle A. Chiles Research Institute.
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