What is it?
ACP-196 is a second generation Bruton’s tyrosine kinase (BTK) inhibitor that can be taken orally. It was developed as an alternative to ibrutinib and was designed to be more selective in targeting BTK. Like ibrutinib it inhibits BTK, a protein important in the development, activation, proliferation, and survival of B-cells. ACP-196 is currently being investigated as a treatment for various B-cell lymphomas, as well as chronic lymphocytic leukemia (CLL).
How does ACP-196 work?
ACP-196 works by inhibiting the activity of BTK, a protein important in the development of B-cells. By preventing the activation of the B-cell antigen receptor signaling pathway, it slows down the growth of cancerous B-cells caused by the overactive BTK.
Does ACP-196 have any side effects?
The side effects for ACP-196 are acceptable and manageable with very few side effects being considered severe.
What is the difference between ACP-196 and ibrutinib?
ACP-196 and ibrutinib are similar in that they both inhibit BTK using the same binding site. They also are both effective in treating chronic lymphocytic leukemia cells. The difference is that ACP-196 inhibits fewer off target enzymes. By being more specific for BTK, the drug may have fewer side effects than ibrutinib, while maintaining similar anti-cancer activity.
How can I access ACP-196?
There are currently numerous clinical trials opened at Weill Cornell Medicine that use ACP-196 for various indications of CLL and B-cell lymphomas. A full list can be found on our Joint Clinical Trials website.
Earlier today the prestigious journal Cancer Discovery published the results of our program’s latest work in mantle cell lymphoma. Although previous clinical trials have demonstrated the effectiveness of ibrutinib in treating patients with mantle cell lymphoma, researchers also noted that some patient’s lymphoma developed ibrutinib resistance during treatment. Our findings revealed some insight into why this resistance occurs and offers several potential treatment strategies for patients who develop ibrutinib resistance. Based on their findings,
“…the researchers devised two treatment strategies that they tested in lymphoma cell lines. Both involve serial use of two anti-cancer drugs — the first to weaken or “prime” the cancer cells, and the second to deliver an added impact. Both use the experimental agent palbociclib (which selectively inhibits two cell-cycle promoting proteins, CDK4 and CDK6) to slow down the cancer’s growth and sensitize cells to the killing power of a second drug.”
As the study’s lead researcher, Dr. Selina Chen-Kiang commented,
“While for many patients ibrutinib represents a valuable treatment option, it has limitations, and we have been able to demonstrate how novel therapy combinations that target the cancer’s resistance pathways might possibly work better.”
These results build on years of laboratory and clinical work at WCMC, and they highlight the need for further research such as our ongoing trial with ibrutinib plus palbociclib
If you have any questions please contact us and look to our clinical trials page for our ongoing trials.
For additional information see the press release from the American Association for Cancer Research.
By Peter Martin, MD
Update: this study is closed to enrollment.
Arguably the most exciting news to come from the American Society of Hematology (ASH) meeting this year was the presentation by Dr. Michael Wang of preliminary results from the phase 2 trial of PCI-32765 for patients with previously treated mantle cell lymphoma (MCL). PCI-32765 is an oral (pill form) inhibitor of an enzyme called Bruton’s Tyrosine Kinase (BTK). BTK plays an important role in communicating pro-survival signals from the cell microenvironment to the nucleus of the cell. Inhibition of BTK by PCI-32765 demonstrated promise in patients with MCL in a national phase 1 that was open at Weill Cornell Medical College. This phase 2 study, also open at Weill Cornell, demonstrated a response rate of approximately 60-70% with little toxicity (mostly mild gastrointestinal side-effects). It is too early to determine how long these effects will last or whether there are any side effects that will become apparent with longer treatment. Click here for more information about this trial.
Dr. Beata Holkova presented the results of a National Cancer Institute (NCI) phase 2 study that was open at several institutions across the country, including Weill Cornell. The trial evaluated the combination of bortezomib (FDA-approved for treatment of patients with previously treated MCL) plus the histone deacetylase inhibitor vorinostat. The combination demonstrated synergistic activity in preclinical studies and showed promised in earlier trials in patients with multiple myeloma. Preliminary results from this NCI trial were encouraging, particularly in the group of patients with MCL that had never been treated with bortezomib. The trial is ongoing. Click here for more information about this study.