Dr. Kerry Rogers on an Upcoming Phase I Clinical Trial of CDK9 Inhibitor VIP152 for Chronic Lymphocytic Leukemia (CLL)
This content was current as of the date it was released. In science and medicine, information is constantly changing and may become out-of-date as new data emerge.
You may notice a new feature on the CLL Society website, a Clinical Trial Banner on our home page.
As many readers already know, I am alive today and CLL free by flow cytometry because I entered two different Phase I clinical trials.
The first trial offered PCI-32765, now know as ibrutinib or Imbruvica at Ohio State University and the second was a CAR-T trial with JCAR-14 at the Seattle Cancer Care Alliance/ Hutch. You can read about my CART trial on my blog here.
I am certain that if I hadn’t been an “early adopter” and hadn’t entered trials using investigational therapies, but instead had relied on standard of care with commercially available medications, I wouldn’t be alive today to write this article.
The first trial we are featuring is sponsored by Sunesis, which is trying to bring a new and potentially important medication, Vecabrutinib or SNS-062, to patients. Here is an earlier discussion of the trial.
Vecabrutinib blocks BTK (Bruton’s Tyrosine Kinase) but in a different way from ibrutinib. Blocking BTK turns off the B-cell receptor (BCR), which is the raison d’être for B cell whose lives are driven to communicate with other cells.
CLL cells are particularly addicted to BCR signaling, and when it is blocked they eventually die. That is a very good thing.
Ibrutinib turns off that BCR communication by covalently binding to BTK, which is a critical part of the BCR pathway.
But some CLL cells can eventually mutate in a way that prevents ibrutinib from binding to BTK, specifically a mutation in C481. This significantly reduces ibrutinib’s efficacy, usually leading to relapse.
Vecabrutinib binds to BTK in a different non-covalent way that should work even when patients develop the C481 mutation and their CLL starts to progress on ibrutinib. This is based on strong preclinical evidence that it turns off the BCR pathway equally well with or without the presence of a C481 mutation.
We are excited as we see the new clinical trial banner as multiple wins:
- Patients learn about a new clinical trial option that might make good sense for those who progress on ibrutinib where choices are limited.
- Increased accrual may accelerate the progress of any new medication towards approval for any who might get a good response.
- Sunesis or any pharmaceutical company benefits by moving their drugs towards commercial success.
- The CLL Society gains exposure and resources that allow us to offer more free services.
We welcome your feedback about this new feature. While we have no plans to allow marketing of drugs on our website, we believe that increasing awareness of clinical trials is completely consistent with our mission and will do what we can to promote important new clinical trials.
Stay strong. We are all in this together.
Brian Koffman
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