Promising New Combination Therapy May Pave the Way for Targeted Treatment in Non-Hodgkin Lymphoma
PHASE ONE Foundation has awarded Dr. Lisa Giulino Roth at Weill Cornell Medicine $360,865 to fund a Phase I trial investigating a new combination therapy for patients with relapsed and refractory non-Hodgkin lymphoma.
Non-Hodgkin lymphomas contribute to 77,000 new cancer diagnoses annually in the US.
The current standard treatment is chemotherapy, which exhibits limited effectiveness and notable toxicity. The need for targeted, chemotherapy-free approaches is clear.
Recent advancements in genetic sequencing have provided insights into the unique vulnerabilities of non-Hodgkin lymphomas. Dr. Roth's research identified specific genetic subtypes responsive to a combination of two non-chemotherapy drugs: venetoclax, targeting a cell death regulatory protein, and tazemetostat, focusing on the epigenome. Both medications have been studied in patients with leukemia and lymphoma and have been shown to be safe, however, they have not previously been used in combination.
This combined approach has the potential to revolutionize treatment by precisely targeting the molecular pathways crucial to cancer cell development, progression, and survival—which could potentially enhance efficacy compared to using either medication alone.
“This combination offers the potential for a chemotherapy-free treatment approach for two of the most common types of non-Hodgkin lymphoma,” said Dr. Lisa Giulino Roth, Associate Professor of Pediatrics at Weill Cornell Medicine and Director of Pediatric Oncology at NewYork-Presbyterian Komansky Children’s Hospital.
Dr. Roth’s preclinical research showed promising results of this combination therapy, eradicating the tumors in mouse models.
Building on this momentum, the primary objective of the trial is to assess the safety and tolerability of the combination treatment for patients with non-Hodgkin lymphomas (specifically patients with either diffuse large B-cell lymphoma or follicular lymphoma) whose disease has returned after having received prior treatment (relapsed), or whose disease has failed to respond to prior treatments (refractory).
To achieve this, Dr. Roth will conduct a two-part clinical trial where patients will ingest oral medication and attend regular clinic visits for blood tests and imaging to oversee potential side effects and track the progression of cancer.
Part 1 involves a dose escalation of venetoclax to identify the optimal dose to be given with tazemetostat– maximizing the therapeutic benefits while minimizing severe side effects. Part 2 will focus on expansion cohorts to further characterize the safety and tolerability of the combination and evaluate early signs of efficacy.
PHASE ONE’s grant provides funding for Part 2 of the trial, and expansion to three additional sites, which will help increase patient accrual.
“This novel combination therapy potentially creates an innovative way to treat non-Hodgkin lymphoma. This exciting approach may provide patients with fresh treatment choices, aiming directly at the crucial molecular pathways driving cancer growth. It's a powerful step forward, offering hope for a brighter and more personalized journey towards recovery,” said Amanda Salvado, MD, PHASE ONE Granting Co-Chair.
This study has the potential to advance treatment for non-Hodgkin lymphomas while avoiding toxic chemotherapy for patients in need of new and better therapeutic options.
The trial is currently open to enrollment– click here to learn more about eligibility.