Medically reviewed by Dr. Brian Koffman
The Bottom Line:
NX-5948 is a new type of drug known as a BTK degrader, and it has promising early clinical data. This phase 1 clinical trial is currently open and recruiting patients with relapsed / refractory CLL, and it may especially interest patients who have developed resistance to BTK inhibitors.
Who Performed the Research and Where Was it Presented:
Dr. Alexey Danilov from City of Hope National Medical Center and colleagues presented the study design at the American Society for Hematology (ASH) Meeting 2023.
Background:
Bruton tyrosine kinase (BTK) is a critical protein for the survival and proliferation of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) cells. Therapies that inhibit BTK (ibrutinib, acalabrutinib, zanubrutinib, pirtobrutinib) have successfully treated CLL / SLL. However, patients who are on BTK inhibitors for a long time eventually can develop resistance mutations to these therapies. BTK degraders are a new class of drugs that grab BTK and shuttle it to the proteosome, which is like the garbage disposal of the cell, where it is destroyed. They can recognize and destroy both normal and mutated BTK. NX-5948 is a new BTK degrader that is being tested in clinical trials.
Methods and Participants:
This is an ongoing phase 1 clinical trial of NX-5948, an oral medication, for patients with relapsed / refractory CLL or non-Hodgkin’s lymphoma. Patients must have had two or more prior lines of therapy.
Results
- Currently, the study is in the dose-escalation phase, where the dose patients receive is gradually increased to see what side effects develop.
- Thus far, 14 patients are enrolled in the trial, and no dose-limiting toxicities have been observed.
- The most common side effects thus far are bruising (57%), nausea (36%), and low platelet counts (36%).
- It is still very early in the study, with a median treatment duration of under three months.
- Rapid and sustained degradation of BTK was observed in all patients.
- Some patients have seen partial responses, which is very encouraging early in the trial. However, with ibrutinib, it can take years to achieve a complete response.
- Clinical responses seem to happen quickly, with changes in lymph node size seen within two weeks.
Conclusion:
While it is still very early on, the safety and efficacy data from this trial of NX-5948 is promising so far, with no significant dose-limiting toxicities and rapid clinical responses. BTK degraders are an exciting new therapeutic area for patients with CLL / SLL, and protein degraders, in general, may enable researchers to target new proteins previously considered too difficult. We look forward to bringing you updates as the trial progresses.
If you are interested in participating in this clinical trial, more information can be found here: A Study of NX-5948 in Adults With Relapsed/Refractory B-cell Malignancies.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Initial Findings from a First-in-Human Phase 1a/b Trial of NX-5948, a Selective Bruton’s Tyrosine Kinase (BTK) Degrader, in Patients with Relapsed/Refractory B Cell Malignancies.
Take care of yourself first.
Ann Liu, PhD
