What are the Recent Updates on BTK Degraders for CLL/SLL?

Explore recent updates on clinical trials investigating BTK degraders for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).

BTK Degraders for CLL/SLL

BTK degraders represent a new class of medicines currently being studied in clinical trials for the treatment of CLL/SLL. 

Unlike traditional BTK inhibitors that only block the activity of the BTK (Bruton's tyrosine kinase) protein, BTK degraders are designed to completely eliminate the protein. This approach aims to halt the growth of CLL cells, including those resistant to BTK inhibitors caused by BTK mutations, potentially overcoming resistance and offering a more durable treatment option for CLL patients.

Ongoing research is exploring various BTK degraders for CLL, with several study updates presented at the 2024 ASH conference. In the article below, we've summarized the key takeaways, so you can stay informed about the newest advances in CLL treatment. If you'd like to explore more articles like this one, don't forget to visit HealthTree News for valuable information and support.

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BTK Degraders NX-2127 and NX-5948

A phase I study explored the BTK degraders NX-2127 and NX-5948 (Nurix Therapeutics), providing valuable insights into their potential for treating CLL and their impact on the immune system.

Phase I trials are designed to assess a treatment's safety, determine the appropriate dosage, and evaluate its initial effectiveness against the cancer. To learn more about how clinical trials work, click here. 

In this study, both NX-2127 and NX-5948 were shown to degrade BTK in CLL cells. Additionally, NX-2127 demonstrated a unique benefit: it enhanced the function of patients' cancer-fighting T-cells, helping to reverse the immune suppression commonly seen in individuals with CLL. This effect was not observed with NX-5948. These promising findings support further research into BTK degraders for CLL treatment.

If you are interested in joining the study to receive NX-2127, click here to review your eligibility.

Watch an interview with Alexey Danilov, MD, PhD, from the City of Hope Cancer Center, as he shares updates on these BTK degraders.

BTK Degrader BGB-16673

The phase 1 CaDAnCe-101 trial evaluated the BTK degrader BGB-16673 in 49 patients with CLL/SLL. In the patient group, 63% of patients had the high-risk type del(17p)/TP53 mutation, and 82% of patients had unmutated IGHV.  

Before receiving BGB-16673, patients had undergone an average of four prior therapies, such as BCL-2 inhibitors, covalent BTK inhibitors, and non-covalent BTK inhibitors. Treating this group of patients with BTK degraders underscores the importance of introducing a new treatment option for those who cannot use other drug classes due to BCL-2 or BTK mutations.

How Effective is BGB-16673 for Relapsed/Refractory CLL/SLL?

This study is still ongoing, but 7.9 months after starting treatment:

• Overall response rate:
  • 78% of patients experienced a partial or full reduction in cancer signs and symptoms
  • When the dose was increased to 200 mg, the overall response rate rose to 94%
• Time to response: On average, patients began to see results within 3 months
• Effectiveness in different patient groups: The treatment was effective in patients with and without prior BTK mutations
• Safety: Most patients experienced mild to moderate side effects, commonly including fatigue, bruising, lower white blood cells (increased risk of infections), and diarrhea 

Early results from the CaDAnCe-101 trial suggest that BGB-16673 is both effective and safe, even in patients who have undergone multiple prior treatments or experienced Richter transformation.

The study is ongoing for patients with CLL/SLL who have previously received a BTK inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) and venetoclax. If you are interested in joining and receiving BGB-16673, click here to check your eligibility.

Summary 

Research updates from the 2024 ASH conference spotlight the potential of BTK degraders as a new treatment for CLL and SLL. Unlike traditional BTK inhibitors, which block BTK activity, these degraders eliminate the BTK protein entirely, offering a promising solution to overcome treatment resistance.

Early-phase clinical trials of BTK degraders—such as NX-2127, NX-5948, and BGB-16673—have shown encouraging results. These include effectiveness against CLL/SLL and manageable side effects, even in patients who are heavily pretreated or considered high-risk. 

If you would like to receive a BTK degrader, click one of the trial page links above or consult your CLL specialist to explore clinical trials you may qualify for.

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Sources: 

• Nx-2127 and Nx-5948, Two Clinical Stage Cereblon-Recruiting BTK Degraders, Facilitate T Cell Functionality in Chronic Lymphocytic Leukemia
• BTK Degrader Study Shows Promise for a New Class of CLL Therapies
• Preliminary Efficacy and Safety of the Bruton Tyrosine Kinase Degrader BGB-16673 in Patients with Relapsed or Refractory Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Results from the Phase 1 CaDAnCe-101 Study
• Efficacy and Safety of the Bruton's Tyrosine Kinase (BTK) Degrader NX-5948 in Patients with Relapsed/Refractory (R/R) Chronic Lymphocytic Leukemia (CLL): Updated Results from an Ongoing Phase 1a/b Study