According to a recent article, a study looking at an investigational BTK degrader proved to have important results in patients with chronic lymphocytic leukemia.
Chronic Lymphocytic Leukemia (CLL)
Chronic lymphocytic leukemia (CLL) is a type of cancer of the blood and bone marrow (the spongy tissue inside bones where blood cells are made). Leukemia in particular is cancer of the white blood cells, which help the body fight infections. Those with leukemia have bone marrow that produces abnormal white blood cells that then crowd out healthy blood cells. In CLL, there are too many lymphocytes, a type of white blood cell. CLL is the second most common type of leukemia in adults.
Symptoms:
Many patients with CLL show no early symptoms, but those who develop symptoms later may experience:
- Enlarged, painless lymph nodes
- Fatigue
- Fever
- Pain in the upper left portion of the abdomen, which may be caused by an enlarged spleen
- Night sweats
- Weight loss
- Frequent infections
Nurix Therapeutics, Inc. Study
The study involved NX-2127, a novel orally-taken degrader of Bruton tyrosine kinase (BTK). Lymphoma and leukemia cells survive through the BTK enzyme in B-cell development, differentiation, and signaling. NX-2127 was used to degrade BTK since it carries the normal cellular protein degradation mechanism.
The phase 1 dose-escalation study was done by Nurix Therapeutics, Inc. Their goal was to investigate the tolerability and safety of NX-2127 in patients that have B-cell malignancies. Patients with such malignancies include those with chronic lymphocytic leukemia, small lymphocytic lymphoma, mantle cell lymphoma, and more.
The coprimary endpoints of the study were defined as concluding the number of patients who experienced severe toxicities, determining the maximum dose that is tolerated by patients, objective response rate, and the observation of patients who experienced adverse events or laboratory abnormalities.
The study’s secondary endpoints were pharmacokinetics, response duration, progression-free survival, overall patient survival, more safety and tolerability evaluations, and complete response rate.
Results
Either 100 mg or 200 mg of NX-2127 was given to patients with CLL/SLL with no BTK C481 and patients with CLL or SLL with a BTK C481. The results showed that in all patients the agent led to a significant decrease in the BTK levels in peripheral blood (fluid that travels through the heart, arteries, capillaries, and veins) from day 1. As the dosing period continued, the study showed continued BTK level suppression.
At the 100mg or 200mg levels, there were no dose-limiting toxicities observed with NX-2127. So far, the oral drug seems to be well-tolerated by patients.
Due to the data from the study being so positive, the study remains ongoing and is actively recruiting more patients who have relapsed or refractory B-cell malignancies. Patients who participate must be 18 years old or older with measurable disease, an -ECOG performance status of 0 or 1, fair organ and bone marrow function, treated with 2 prior lines of therapy, and require systemic therapy.