ASH 2021: A Phase 1a/b Dose Escalation Study of the Mutation Agnostic BTK/FLT3 Inhibitor Luxeptinib (CG-806) in Patients with Relapsed or Refractory B-Cell Malignancies

INTRODUCTION:

Treatments for Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma (CLL / SLL) are being developed to address refractory cases, in other words, those that no longer respond to current therapies.

In this study presented at the American Society of Hematology Annual Meeting and Exhibition (ASH 2021), the results of early (phase 1a/b) trials on Luxeptinib in 23 patients are reviewed.

TAKEAWAYS:

• Luxeptinib inhibits several enzymes or kinases involved in B cell receptor (BCR) signaling pathways needed for cancer cells to survive in patients with CLL / SLL, such as:
  • BTK (Burton Tyrosine Kinase)
  • ERK (Extracellular Signal-regulated Kinase)
  • SYK (Spleen Tyrosine Kinase Receptor)
• The 21 patients studied had failed at least three prior treatments. (range 1-12)
• Eleven of the 23 patients studied had CLL, and the rest had other B-cell lymphomas. One had Richter’s Transformation, a serious complication in 5-10% of CLL patients.
• Response and side effects were monitored at various dosages.
• Dosages were given twice a day in 28 cycles with increasing dosages of 150 mg, to 300mg, to 450 mg, and 600 mg. Results for the 750 mg dose are pending.
• Patient side effects of the more severe category 3 or higher included:
  • Increased or decreased white blood cell counts
  • Neutropenia, or decreased neutrophils (cells that fight infection)
  • Anemia
  • Decreased platelets (cells that regulate bleeding and clotting)
  • Diarrhea, headache, liver function test abnormality, and one case of hypertension.
• At dosages of 300mg or higher, multiple anti-cancer targets were inhibited.
• Imaging obtained in 3 SLL and 1 CLL patients showed decreased lesion size with Luxeptinib treatment.
• Early results show Luxeptinib appears to be an effective and safe therapy.

CONCLUSIONS:

Luxeptinib is one of many new treatments currently being studied for patients who have failed other treatments.   Early results are promising for both effectiveness and safety. We need new options for patients when the present excellent but limited classes of therapies are no longer working.  Luxeptinib is one such possible option.

CLOSING:

Here is the link to this presentation: A Phase 1a/b Dose Escalation Study of the Mutation Agnostic BTK/FLT3 Inhibitor Luxeptinib (CG-806) in Patients with Relapsed or Refractory B-Cell Malignancies

For information on ‘ ‘Richter’s Transformation see: https://cllsociety.org/2020/01/ash-2019-dr-john-allan-on-richters-transformation-in-cll-chronic-lymphocytic-leukemia/

For information about drugs that target SLL/CLL signaling pathways, see:

BCR inhibitors:

https://cllsociety.org/2020/01/iwcll-2019-dr-jan-burger-on-targeting-the-b-cell-receptor-bcr-in-chronic-lymphocytic-leukemia-cll/

BTK inhibitors:

https://cllsociety.org/2020/08/what-you-need-to-know-about-btk-inhibitors-as-treatment-for-your-your-loved-ones-cll-2/

SYK inhibitors:

https://cllsociety.org/2020/05/ash-2019-dr-alexey-danilov-and-dr-john-pagel-discuss-new-drug-targeting-syk-pathway-provides-hope-when-used-in-combination-with-obinutuzumab/

Hopeful treatment options are becoming available for SLL/CLL patients that have failed other therapies.

Stay positive and safe.  We are all part of an excellent organization for hope, help, and education.

Michael Green MD and CLL patient