The Alliance for Clinical Trials in Oncology has launched a new clinical trial for adults who need first-line therapy for chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). The study (Alliance A042302) will explore whether combining two targeted medicines, zanubrutinib and sonrotoclax, can effectively send cancer into remission, allowing patients to discontinue treatment until there is evidence the cancer has recurred.
For decades, people diagnosed with CLL or SLL have often faced the reality of long-term or even lifelong cancer treatments, as these slow-growing cancers tend to recur frequently, requiring additional maintenance therapies. Despite high survival rates (about 94% of patients live five years after diagnosis), the burden of ongoing therapy can deeply affect the lives of patients and their families. That’s where this new study hopes to make a difference. The study aims to find out whether these two targeted cancer pills can work together to control CLL/SLL so effectively that some patients may be able to stop treatment earlier, based on how their disease responds.
“Because CLL and SLL are such slow-growing but treatable cancers, many patients must undergo regular treatments for years to keep their cancer at bay,” said Jennifer R. Brown, MD, PhD, the Worthington and Margaret Collette Professor of Medicine in the Field of Hematologic Oncology at Harvard Medical School, Director of the CLL Center of the Division of Hematologic Malignancies at Dana-Farber Cancer Institute, and study chair of this trial. “If successful, this new treatment plan could prove to be life-changing for these individuals. The ability to dramatically reduce the number of ongoing appointments, treatments, side effects and co-pays would give patients and their families much more freedom to enjoy their lives, despite a diagnosis of cancer.”
Unlike traditional chemotherapy, which attacks rapidly dividing cells throughout the body, zanubrutinib and sonrotoclax are targeted therapies, designed to block specific survival mechanisms that cancer cells depend on. Already FDA‑approved, zanubrutinib is a BTK inhibitor, meaning it shuts off an internal “grow” signal that CLL/SLL cells use to multiply. Sonrotoclax (BGB‑11417) is an investigational drug that blocks a protein called BCL‑2, that cells need to grow.
Together, the drugs approach cancer cells from two sides: one slows their growth and the other encourages them to die. For some patients, this combination may be powerful enough to clear the disease to the point where it becomes undetectable, a milestone known as undetectable measurable residual disease (MRD). When MRD is undetectable, patients can stop treatment, often for months or years at a time.
Participants in the study will be randomly assigned to one of two groups:
After about 15 months, patients in the combination group will undergo testing to see if their cancer has entered remission. If no cancer cells are detectable, they may be able to stop treatment entirely, an outcome that could be life-changing for older adults living with chronic cancer.
This phase III trial aims to enroll about 450 adults over age 65 who have not already been treated for CLL or SLL.
For more information on Alliance A042302: Phase III evaluation of fixed duration zanubrutinib plus sonrotoclax-based therapy compared to continuous zanubrutinib in previously untreated older patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), visit ClinicalTrials.gov .
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The Alliance for Clinical Trials in Oncology is a national leader in advancing cancer research, uniting more than 25,000 cancer specialists at 115 main institutions and 1,400 affiliates across the U.S. and Canada. As part of the National Clinical Trials Network and a leading research base for the NCI Community Oncology Research Program, the Alliance conducts pioneering, practice-changing clinical trials that improve outcomes and reshape standards of care. Its work has led to multiple FDA approvals, influenced national guidelines, and produced hundreds of high-impact publications. More than 40,000 participants have taken part in Alliance studies, and its growing biospecimen repository now includes more than 1.5 million samples, collected over the past 30 years. Learn more at www.AllianceforClinicalTrialsinOncology.org .