This Phase 1/2 trial was designed to evaluate the safety profile and efficacy of orally administered ACP-196 in patients with relapsed or refractory CLL/SLL. ACP-196 is a second generation BTK inhibitor that is more selective than the first generation BTK inhibitor ibrutinib. Bruton’s tyrosine kinase (BTK) is an enzyme involved in B cell receptor pathway signaling that has been shown to be critical for CLL cell survival. Trials with ibrutinib established BTK as an effective therapeutic target for the treatment of CLL.
As part of the trial, patients were treated continuously with escalating doses of ACP-196, once or twice daily. No dose limiting toxicities were identified and 100 mg twice daily was established as the most efficacious dose. The median age of the patients and number of prior therapies were 62 years and 3 prior therapies respectively. The median time on the study was 10.3 months. As of June 2015 there were 60 patients who were evaluable for response.
The overall response rate was 93% for all patients and 100% in the deletion 17p patient. ACP-196 was well tolerated, with 93% of patients remaining on treatment. The most common adverse events were headache and diarrhea. No disease progression has occurred to date.
“This is a critical time for treatment in CLL because we are witnessing a change in treatment paradigms. We are for the first time seeing the opportunity to move completely away from a dependence on chemotherapy. These new treatments are highly effective and well tolerated. Three new treatments that have recently been approved include ibrutinib, idelalisib and obinutuzumab. There are also two second-generation BTK inhibitors that work similar to ibrutinib and are well tolerated that are in the pipeline,” Dr. Furman said. Regarding the new agents, Dr. Furman makes it clear. “Not only are they preferable because they are better tolerated but because they are also far more effective. Going forward, there is an eye toward not only short term toxicities, but also long- term health. As we continue to identify new agents, the possibility of living a long and full life with minimal toxicity is real for CLL/SLL patients, which is exciting.”
The new treatments for CLL/SLL are currently open in clinical trials. You can follow the link to our clinical trials website to see which trials are available for CLL/SLL.