James Dean, MD, PhD, Shares MRD Outcomes of Ibrutinib Plus Venetoclax for First-Line Treatment of CLL

James Dean, MD, PhD, discusses minimal residual disease outcomes after fixed-duration ibrutinib plus venetoclax versus chlorambucil plus obinutuzumab for first-line treatment of CLL.

Transcript:

Hi, my name is Jim Dean. I'm an executive medical director with Pharmacyclics, an AbbVie company, and I'm the Imbruvica Global Development Lead.

Today, I will discuss the GLOW study and CAPTIVATE study, which involve combined ibrutinib plus venetoclax. 

The GLOW study is a randomized phase 3 study that compared ibrutinib plus venetoclax versus chlorambucil and obinutuzumab. The CAPTIVATE study is a large phase 2 study in a younger patient population with high-risk features, with more than one cohort in evaluating different strategies with ibrutinib plus venetoclax.

These studies were initiated based upon the established efficacy of ibrutinib in patients with CLL, and very interesting preclinical data suggesting that the combinations could result in an even greater clinical benefit for patients than either agent alone. This combination had been initially tested in a very near timeframe with multiple clinical studies around the world.

The CAPTIVATE study, headed by the Pharmacyclics side of our partnership and the GLOW study run by the Janssen Biotech, Inc., side of our partnership with Imbruvica are the company-sponsored studies that we're using to better understand this combination's potential benefit for patients.

The GLOW study compared the ibrutinib plus venetoclax versus the chlorambucil-obinutuzumab combinations. It was in younger patients who had comorbidities or challenges getting more aggressive therapies.

The study was run globally, and the primary endpoint was progression-free survival (PFS). There was a very clear statistically significant improvement in PFSl with I plus V compared to the G plus C combination. At ASH 2021 we updated the PFS data while also looking more deeply at the minimal residual disease outcomes.

Minimal residual disease is a way to scientifically assess how much cancer is left in the patient at the end of treatment because both of these treatments are given as a fixed duration where treatment stops and then the patient is monitored over time.

What was shown was that, at least at this point, the MRD status, whether you were positive or negative at the end of treatment, your PFS still looks very outstanding.

The other interesting thing was looking, with a more sensitive technique, at the minimal residual disease and showing that the I plus V combination is achieving much deeper responses than G plus C and more frequently than G plus C.

This is not unexpected, but it's very gratifying and very helpful to support the potential clinical benefit, particularly as we're seeing for PFS. Hopefully, these deeper responses will lead to longer remissions.

The CAPTIVATE study, we did an update with an additional year of follow-up. The primary analysis of what we call the MRD cohort was presented at ASH 2020. This year, we presented an additional year of follow-up.

In that study, patients who achieved a deep response as assessed by this undetectable minimal residual disease in a confirmed approach were randomized to either placebo or no treatment or to continue ibrutinib.

The exciting thing was that both arms had a very similar durability of response, even a year ago. With one additional year of follow-up, there were no new events. All of the patients had continued to be free from MRD relapse as well as free from progression and of course death. This is really exciting.

The CAPTIVATE safety was updated, demonstrating the safety of the combination and the events that are seen with continued treatment as well as no treatment. Together, CAPTIVATE and GLOW, addressing a broad spectrum of patients and showing the value of ibrutinib plus venetoclax as fixed duration in these patient populations.

Right now, of course, Imbruvica is given as a continuous single agent until progression or intolerability, and venetoclax is given in combination with other agents. It's hoped that this new combination may provide additional efficacy benefit, may have different toxicity profiles so that's more tolerable for some patients.

We hope that we'll be able to take this to regulatory agencies to get approvals so that patients in the United States, in Europe, and around the world will have access to this fixed duration approach. Instead of an Imbruvica continuous treatment, they'll be able to have approximately 15 months of treatment and then be able to come off therapy and enjoy that treatment-free interval.

I think that with this work with ibrutinib plus venetoclax, what we're doing is seeking new treatment options for patients so that each patient has the opportunity to choose the treatment that works best for them, for their lifestyle, for their values.

We're very excited about it because the results that we're seeing offer a lot of promise. It adds to the breadth and the depth of Imbruvica data that we've accumulated since our first approval in 2013 across multiple indications.

In addition to the CLL/SLL, I'll just mention that we're also investigating this combination in multiple other indications, such as mantle cell lymphoma, and it's been investigated both by investigators and others around the world, also for Waldenstrom's macroglobulinemia and other indications. We're very excited about it.