June 16, 2020:

A Big Ten Cancer Research Consortium phase Ib study, led by the University of Michigan Rogel Cancer Center, will test the maximum tolerated dose and response rate of the PI3K alpha/delta inhibitor copanlisib in combination with the immunotherapy agents nivolumab and rituximab in adults with relapsed or refractory follicular or marginal zone indolent lymphoma. The study is now open to accrual at the University of Michigan.

Follicular lymphoma is the second most common non-Hodgkin lymphoma (NHL), with approximately 15,000 cases diagnosed in the United States per year. Indolent lymphoma is a subtype of NHL that grows and spreads slowly in the lymphatic system.

While advances in progression-free survival and overall survival have increased in patients with follicular lymphoma, 20 percent of patients experience disease progression within the first two years of first-line therapy.

The study, BTCRC-LYM17-145, a phase Ib dose de-escalation study of the PI3K alpha/delta inhibitor copanlisib given in combination with the immunotherapeutic agents nivolumab and rituximab in patients with relapsed/refractory indolent lymphoma, will test the maximum safe dosage and response rate of this combination of drugs.

“The goal is to see if the combination is safe, but also to see if we can improve upon the response rate,” said Tycel Phillips, MD, sponsor-investigator of the study and a medical oncologist at the University of Michigan Rogel Cancer Center. “The drugs have been looked at in other settings, but not particularly in follicular lymphoma or marginal zone lymphoma.”

Dr. Phillips said researchers hope to improve the overall response rate and the duration of response, while offering a safe treatment and a chance to improve patients’ quality of life.

Copanlisib is a pan-class phosphoinositide 3-kinase (PI3K) inhibitor and is approved by the U.S. Food & Drug Administration (FDA) to treat follicular lymphoma patients who have received at least two prior treatments for their disease. Copanlisib blocks several enzymes that promote cell growth.

Nivolumab is an immune checkpoint inhibitor that stimulates the body’s immune system to fight cancer cells. In a healthy person, T cells in a human body help the immune system fight infections and diseases. However, in cancer, cells can hide from T cells and take over a pathway called PD-1. This drug is designed to block the PD-1 pathway so the immune system can recognize and kill cancer cells. Nivolumab is FDA-approved to treat many cancers, including lung cancer, head and neck cancers, colorectal cancer, melanoma, liver cancer, kidney cancer, bladder cancer, and Hodgkin lymphoma.

Dr. Phillips said researchers hope that by blocking the PD-1 pathway they can create “a more robust, natural response and enhance copanlisib.”

Rituximab is an antibody that helps the body’s immune system fight cancerous B cells. Rituximab is approved by the FDA to treat non-Hodgkin lymphoma, chronic lymphocytic leukemia, and other conditions including rheumatoid arthritis, granulomatosis with polyangiitis, microscopic polyangiitis, and pemphigus vulgaris.

The combination of copanlisib with nivolumab and rituximab is not FDA-approved to treat this type of cancer and should be considered investigational.

The study is supported by Bayer Healthcare Pharmaceuticals Inc. and Bristol-Myers Squibb.

Blood and tissue will be collected to support correlative research. Investigators plan to explore PD-L1 expression on malignant and surrounding stroma cells in the primary tumor, to evaluate changes in T cells in response to the treatment, and to determine if the pre-treatment interferon-gamma gene signature score predicts a response.

“Part of the correlative research is looking to see what changes we’re inducing in the patients in the tumor microenvironment and also within the immune cells in that area, to see if we’re actually modulating the immune response and improving the response rate that we’re seeing,” Dr. Phillips said. “We have seen that patients are living a lot longer than they had a few decades ago, so we are moving toward hopefully making this a true chronic disease — a disease that, if we can’t get rid of, patients can live with.”

Up to 35 subjects may participate in this clinical trial. To qualify for the study, participants must be adults age 18 and older with relapsed or refractory follicular or marginal zone lymphoma and have received at least one prior line of chemoimmunotherapy. They also should not be a candidate for autologous stem cell transplantation. Participants will be monitored throughout the study and may discontinue treatment at any time in consultation with their oncologist.

For more information about this research study, including full eligibility requirements, visit www.clinicaltrials.gov (study #NCT04431635).

About the Big Ten Cancer Research Consortium: The Big Ten Cancer Research Consortium was created in 2013 to transform the conduct of cancer research through collaborative, hypothesis-driven, highly translational oncology trials that leverage the scientific and clinical expertise of Big Ten universities. The goal of the Big Ten Cancer Research Consortium is to create a unique team-research culture to drive science rapidly from ideas to new approaches to cancer treatment. Within this innovative environment, today’s research leaders collaborate with and mentor the research leaders of tomorrow with the unified goal of improving the lives of all patients with cancer.

About the Big Ten Conference: The Big Ten Conference is an association of world-class universities whose member institutions share a common mission of research, graduate, professional and undergraduate teaching and public service. Founded in 1896, the Big Ten has sustained a comprehensive set of shared practices and policies that enforce the priority of academics in the lives of students competing in intercollegiate athletics and emphasize the values of integrity, fairness and competitiveness. The broad-based programs of the 14 Big Ten institutions will provide over $200 million in direct financial support to more than 9,800 students for more than 11,000 participation opportunities on 350 teams in 42 different sports. The Big Ten sponsors 28 official conference sports, 14 for men and 14 for women, including the addition of men’s ice hockey and men’s and women’s lacrosse since 2013. For more information, visit www.bigten.org.