The Bottom Line:
Enitociclib is an experimental CDK9 inhibitor being developed for the treatment of non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). It is currently being tested for safety in phase 1 clinical trials, and thus far, preliminary data show a favorable safety profile.
Who Performed the Research and Where Was it Presented:
Dr. Mazyar Shadman from Fred Hutchinson Cancer Center and colleagues presented the results at the American Society for Hematology Annual Meeting in 2022.
Background:
Over time, patients with CLL / SLL can stop responding to drugs like ibrutinib (covalent BTK inhibitor) and venetoclax (BCL2 inhibitor). Because patients can become resistant to both drugs (double-refractory), researchers are studying drugs that work through different mechanisms of action. For example, cyclin-dependent kinase (CDK) inhibitors are a class of drugs that work by interfering with the cell cycle pathway, which is necessary for cell growth and division.
In this video, Dr. Javier Pinilla, Senior Member and Head of the Lymphoma Section at Moffitt Cancer Center, interviewed Dr. Mazyar Shadman, an Associate Professor and blood cancer specialist at Fred Hutchinson Cancer Center. They discussed enitociclib, an experimental CDK9 inhibitor in development for treating NHL and CLL.
Methods and Participants:
Enitociclib (a.k.a. VIP152/formerly BAY1251152) is currently being evaluated in two phase 1 clinical trials. In the first trial, patients with solid tumors or aggressive NHL received 30 mg of enitociclib once weekly. In the second trial, patients with relapsed/refractory CLL or Richter syndrome received 10 mg enitociclib for the first week and 15 mg afterward. Enitociclib is administered as a once-weekly IV infusion in 21-day cycles.
Results:
- The data presented here are a pooled safety analysis of 17 patients from both trials.
- Participants included 15 men and two women with a median age of 68 years and a median of 3.5 prior therapies.
- The main side effects observed were mild/moderate gastrointestinal adverse events, fatigue, and fever.
- Low white blood cell counts occurred in 40% of patients, but this was manageable with supportive therapy.
- No high-grade liver toxicities have been observed.
- Thus far, there have not been any discontinuations due to adverse events.
- Three patients died due to disease progression.
- While there does appear to be some clinical activity against NHL, it is still too early to say if this drug has any efficacy against CLL.
Conclusions:
It is still early for enitociclib, but thus far, preliminary data from phase 1 clinical trials show a favorable safety profile in a hard-to-treat patient population. We look forward to learning more about its safety and efficacy as these trials progress.
Links and Resources:
Watch the interview on the abstract here:
You can read the actual ASH abstract here: Enitociclib (VIP152/formerly BAY1251152) Is a Selective and Active CDK9 Inhibitor: Preliminary Safety and Early Signs of Efficacy in Patients with Non-Hodgkin Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)
Take care of yourself first.
Ann Liu, PhD
