CAPTIVATE and iNNOVATE Clinical Trial Results for CLL

Transcript:

Susan M. O’Brien, MD: The CAPTIVATE trial is a frontline trial in CLL, and it’s a combination of ibrutinib (Imbruvica) and venetoclax (Venclexta). There’s no antibody in this trial. The other important point is the trial design, where ibrutinib is given for 3 months first and then venetoclax typically ramp ups to the 400-mg dose, followed by continuous therapy with both drugs. The reason the lead-in is important is that what we do is debulk the patient and reduce the risk for tumor lysis. What the early data from this trial have shown is, in fact, there was no significant clinical tumor lysis at all, and the combination of drugs was very well tolerated. Basically, what you see in terms of a side effect profile are mainly attributable to ibrutinib—some diarrhea, some arthralgias—typically the things we see with ibrutinib. It was a safe and an extremely effective regimen with very high response rates and high levels of MRD negativity in the initial cohort where we have follow-up so far.

The CAPTIVATE trial of ibrutinib and venetoclax is very important because it shows us that there are very high response rates and high levels of MRD negativity in this frontline trial. It also will give us good information on progression-free survival based on MRD status, and it does some other important things. There is a cohort of patients who will be discontinued based on their MRD status, so if they’re MRD-negative, they can come off therapy. Later on in the trial, after an amendment, there was a cohort where, rather than using MRD status to determine whether patients should stop therapy, all patients received a fixed duration of therapy. That will also be very important because that’s how we would like to be treating patients, with fixed duration of therapy rather than continuous therapy.

The iNNOVATE trial looked at ibrutinib in patients with Waldenström macroglobulinemia, and we know that it’s active there, but this trial was specifically for patients with rituximab-refractory disease. These patients have progressed very quickly on rituximab or had failed to respond to rituximab—so a higher risk group. Yet even in this higher-risk group, there was a very high response rate with ibrutinib of 90%. With an 18-month follow-up, the progression-free survival was 86%. These patients are doing great even though they form a higher-risk group with Waldenström than some of the other patients that had previously been treated with ibrutinib.

The clinical significance of the iNNOVATE trial is that we can take patients who failed other therapies, such as rituximab, and still expect very high response rates, as good as in patients who were not so refractory to begin with.

Transcript Edited for Clarity