Investigating Next Steps for Pirtobrutinib Therapy Among Patients With Chronic Lymphocytic Leukemia

Inhye Ahn, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, discusses next steps for investigating applications of pirtobrutinib for treating patients with chronic lymphocytic leukemia (CLL) in earlier settings, including an ongoing phase 2 trial exploring the drug as a first-line treatment.

Transcript:

I'm Inhye Ahn and I'm an assistant professor at Dana-Farber Cancer Institute. My research focus is chronic lymphocytic leukemia. I'm going to talk about the next steps for investigating pirtobrutinib in CLL patients. Pirtobrutinib has been a new exciting class of molecule that has been approved by the FDA as a third-line treatment for CLL or beyond.

What would typically happen in the clinical setting right now is the patient would go through the other targeted agents such as BTK inhibitors and BCL-2 inhibitor venetoclax based therapy, and then when they cannot tolerate these drugs or progress on these drugs, then they would receive pirtobrutinib. The drug has been effective. The response rate has been about 80%, and the duration of response can go up to about 2 years in general.

Because of the effectiveness as well as the favorable safety profile of this drug, there is a huge interest of pushing this drug to a frontline setting. So the key questions are: can we use this drug in an upfront setting of CLL, and can that improve the outcome? Can we also use it in a different way, namely by a fixed-duration therapy, and can we achieve that aim by combining pirtobrutinib with other agents?

One of the approaches that is now being tested in Europe is the CLL-18 trial. This is a trial for the frontline treatment in CLL comparing a conventional venetoclax plus obinutuzumab therapy to pirtobrutinib plus venetoclax therapy. The patient would be randomly assigned to either ven-obin or pirto-venetoclax, and be compared, whether fixed duration therapy with ven-obin would be better or worse than the pirtobrutinib-containing regimen.

In the US, I am leading a multicenter single arm phase 2 study (NCT06333262) testing the pirtobrutinib and obinutuzumab regimen given in a fixed duration of 12 cycles. Everyone who will be coming onto this trial will receive pirtobrutinib, then [pirtobrutinib] in combination with obinutuzumab, then they would stop treatment after 12 cycles. We would monitor our patients every 3 months, and if there is a clinical progression, the patient can be retreated.

What this trial aims to address is: can we stop pirtobrutinib and not include venetoclax, and if we introduce a deliberate treatment break, how long would that be?