Medically reviewed by Dr. Brian Koffman
The Bottom Line:
LP-168 is a new dual covalent and noncovalent BTK inhibitor well-tolerated in a phase 1 clinical trial. This could potentially be an option for patients who have developed resistance to other BTK inhibitors.
Who Performed the Research and Where Was it Presented:
Dr. Jennifer Woyach and colleagues from Ohio State University presented the results at the American Society for Hematology (ASH) Annual Meeting 2023.
Background:
Bruton tyrosine kinase inhibitors (BTKi) are very effective for treating chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) because these cancers are very dependent on the BTK pathway for their survival. LP-168 is a new drug that can bind to BTK covalently (in the same way that ibrutinib, acalabrutinib, and zanubrutinib bind) or noncovalently (in a similar way as pirtobrutinib). This could be useful for treating patients who have developed resistance to other BTK inhibitors.
Methods and Participants:
This is a phase 1 clinical trial testing the safety and dosing of LP-168 in patients with relapsed / refractory B-cell cancers.
Results
- Thus far, 43 patients have enrolled in the trial, including 35 with CLL.
- CLL patients had a median of 3 prior lines of therapy.
- 94% had previously received a covalent BTKi, and 11% had previously received a noncovalent BTKi.
- Because LP-168 is more selective than other BTK inhibitors, fewer side effects were seen.
- The majority of side effects were low grade, and the most common side effects included diarrhea, fatigue, joint stiffness, headache, constipation, cough, and dizziness.
- The overall response rate at all dose levels (ranging from 100 – 300 mg/day) was 55%.
- In patients with both BTK C481 and T474 mutations who received the highest dose level (300 mg/day), the overall response rate was 75%.
Conclusion:
LP-168 is a new dual covalent and noncovalent BTK inhibitor well-tolerated in a phase 1 clinical trial. This could potentially be an option for patients who have developed resistance to other BTK inhibitors. While this particular study is almost closed, there should be opportunities to participate in more extensive clinical trials with this drug in the future.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Initial Results of a Phase 1 Dose Escalation Study of LP-168, a Novel Covalent and Non-Covalent Next-Generation Inhibitor of Bruton’s Tyrosine Kinase.
Take care of yourself first.
Ann Liu, PhD
