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Published on December 7, 2020
Promising New Combination Therapy Unveiled: Umbralisib and Ublituximab
The promising new drug combination of umbralisib plus ublituximab, being referred to as "U2," offers an exciting new chronic lymphocytic leukemia (CLL) treatment option. Dr. John Gribben of the Barts Cancer Institute in London, England joins Patient Power co-founder and CLL patient Andrew Schorr to discuss the unveiling of the UNITY Phase 3 Study, as reported at the 62nd American Society of Hematology Annual Meeting & Exposition (ASH 2020).
This program was supported by an educational grant from TG Therapeutics. This organization has no editorial control. It is produced by Patient Power, and Patient Power is solely responsible for program content.
Transcript | New Drug Combination for CLL Treatment
Andrew Schorr: Welcome to Patient Power. I'm Andrew Schorr, living with chronic lymphocytic leukemia, now 24 years. I'm in Phoenix, Arizona today, but joining us from London, England is one of my favorite hematology experts and that's Dr. John Gribben. He's a Professor and Consultant Medical Oncologist at the Barts Cancer Institute in London. Dr. Gribben, thanks for being with us on Patient Power once again.
Dr. Gribben: Always a pleasure. Andrew, I'll bet you say that you're their favorite to almost everyone you interview but thank you for kind words.
Andrew Schorr: You're my favorite. You and I were talking, and I've known you about a quarter of a century now.
Dr. Gribben: Quarter of a century, absolutely.
Andrew Schorr: Long time. So, John, I'll call you. You've been a leading researcher for a long time in CLL and you've presented the UNITY-CLL Phase III study at the American Society of Hematology (ASH) meeting, which brings people from all over the world, virtually this year. What is this study? Then help us understand what it could mean for CLL patients.
What Is the UNITY Study?
Dr. Gribben: Thanks so much for the opportunity to talk to you today. The UNITY study was a study examining two novel agents. One is umbralisib and the other one is ublituximab and we call that the “U2” regimen, not the pop group here, but these two “U” drugs together.
What Information Is There on Umbralisib and Ublituximab for CLL Treatment?
Umbralisib is a PI3 kinase delta inhibitor – also has some activity against another enzyme called casein kinase 1 epsilon. The trial was taking that umbralisib, the PI3 kinase inhibitor, plus ublituximab. Ublituximab is a next generation rituximab (Rituxan), if you like. It targets CD20, but it's been engineered to have more specific activity to activate other cells that would work well with umbralisib. It also targets a different part of the molecule than rituximab.
We've got these two agents together and the trial itself was comparing these two agents in a phase III study against chlorambucil (Leukeran) and obinutuzumab (Gazyva), which of course is licensed and approved for the treatment of usually a bit more frail people who might not be candidates for things like FCR chemotherapy.
What Are the Clinical Results of This New Treatment Option?
What the study showed was that the novel combination outperformed the chemoimmunotherapy. I guess that we're getting used to that nowadays, that these novel therapies are almost always outperforming chemoimmunotherapy and that's exactly what we see. Now, a really novel component of this study was it enrolled both treatment-naive, that is people who've never been treated, this was their first-line treatment or people who were relapsed and refractory.
The benefit that we saw in the treatment-naive patient population was quite impressive. Twice as good as giving chemotherapy in this setting. In the relapse setting, we also saw it outperformed the chlorambucil arm, although not surprisingly didn't perform quite as well in the relapse setting. The overall response rate with the U2 combination was about 83% and outperformed again the chlorambucil. The duration of response was longer and about 62% of the patients were able to maintain the responses at two years and more than 90% of patients had a response.
The big question everyone's been interested in is umbralisib, is it really different from idelalisib (Zydelig) and duvelisib (Copiktra)? Certainly, the side effect profile suggests that although diarrhea was one of the more common side effects seen with the umbralisib combination, less than 2% of the patients develop this colitis that we've seen with some of these other agents. There wasn't much in the way of that liver toxicity and only one of these patients develop pneumonitis. The colitis and the pneumonitis are the kind of side effect profiles that we're most concerned about with this class of drugs and we aren't seeing that at anything like the same rates.
Well, it means more choices for our patients. It also means we've got to another class of agents that we know are effective that would potentially be able to be used if patients fail the other therapies that are out there. Of course, there were only a relatively small number of patients on this study, only about 15 patients in total who'd had a BTK inhibitor before going on to do this, but almost 60% of those patients still responded when they had failed a BTK inhibitor.
More choice for our patients. That's what we're looking for. Of course, the combinations don't end here. The U2 regimen, now we've shown it can be safe and effective, is now also being explored as a backbone for triplet combinations. There's also presentations at this meeting in poster form of looking at the U2 regimen plus venetoclax (Venclexta) and another one looking at the U2 regimen plus a novel BTK inhibitor. More of these can we bring triplets of therapy together. Overall, we were very pleased to see that the study met its primary endpoint and being able to present it here at ASH.
Andrew Schorr: That's where I wanted to end up with you, Dr. Gribben, is with these combinations and further research that you're helping lead, someone with CLL today can often look forward to, maybe mostly look forward to, a long life.
Dr. Gribben: Yeah. That's absolutely what we're looking for. We're just thinking how recently it was that all we could talk about were really making patients' symptoms better and now we're talking about really lengthening people's life and lengthening the quality of life that they have, too.
Andrew Schorr: Dr. John Gribben from Barts in London, thank you for your leadership with this study, explaining it to us and your continued work for all of us with CLL.
Dr. Gribben: Andrew, always a pleasure to talk to you.
Andrew Schorr: Okay. Andrew Schorr here in Phoenix. Dr. Gribben in London. Remember knowledge can be the best medicine of all.
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