Positioning A New Standard of Care in Relapsed Multiple Myeloma: Q&A with Imran Khan, MD, PhD

Imran Khan, Md, PhD, Vice President of U.S. medical affairs for hematology, oncologist, Johnson & Johnson, in a conversation with Pharmaceutical Executive, discussed the Phase III study of Tecvayli plus Darzalex Faspro, which showed an 83% reduction in the risk of disease progression or death in relapsed/refractory multiple myeloma patients, with a hazard ratio of 0.17.

The study, which led to a late-breaking oral presentation at the American Society of Hematology, demonstrated the combination's transformational impact on patients. The approval came 55 days after filing under the FDA Commissioner's national priority voucher pilot program. Johnson & Johnson's approach emphasizes safety, efficacy, and real-world implementation, aiming to advance curative treatments for multiple myeloma.

A transcript of Khan’s conversation with Pharmaceutical Executive can be found below.

Pharmaceutical Executive: What are the implications of Tecvayli plus Darzalex Faspro demonstrating an 83% reduction in the risk of disease progression or death against a daratumumab-based control?
Imran Khan: So Tecvayli Plus Darzalex Faspro is a Phase III study that we did to look at patients who have relapsed after one line of treatment with multiple myeloma. So these are relapse, refractory patients who have a great unmet need. This study really offered us the opportunity to show the incredible possibility of combining two immunotherapies, and the results have been absolutely amazing.

You cited the 83% reduction in the risk of disease progression or death just to characterize that even more. 83% is an amazing number. It's nearly all your patients. But the hazard ratio we just simply look at very carefully was 0.17 which is nothing short of astounding. We don't see hazard ratios like that in studies, we just don't. We look at hazard ratios that are less than one, so 0.17 was what made this really stand out, and that's where that 83% comes from.

So, you're talking about patients over a period of three years that received this combination therapy, and, not only did they do well, but there was no disease progression, and they did not die. So, that shows how this has completely been transformational in terms of the possibility for an inpatient population with great unmet need. This is what makes the data so compelling, and really what allows us the opportunity to be able to offer a new standard of care for patients in this patient population that is not only efficacious but is also safe to get because safety is so critical for our patients as well.

We looked at different endpoints, we looked across key secondary endpoints, as well as treatment response rates, minimal residual disease, overall survival time to worsening of symptoms, and really the impact of this regiment was across multiple patient measures. And I'm proud to say that, you know, as a culmination of this has led to a late breaking oral presentation at the American Society of Hematology in December of last year.

It has been transformational for patients, for lack of a better word, and if you look at the control, which is a good control, daratumumab-based control, it was not even close in terms of comparison between what Tecvayli Plus Darzalex Faspro offers compared to a standard of care regimen.

PE: What design choices made the MajesTEC-3 trial so clinically compelling, and what does the depth of response data tell us about the potential ceiling for what this combination can do?
Khan: I think the key thing here is to understand that we have taken two amazing immunotherapies that function so well independently, namely Darzalex, which is the first approved antibody in multiple myeloma, CD38 targeting, and then Tecvayli, which is a bispecific that targets another protein called BCMA, and then brings in the immune system T cells to kill the myeloma cells.

Combining these two together with the synergistic effect that they both have has been incredible for patients. So you have the backbone of multiple myeloma therapy, Darzalex, that we developed over 10 years ago now being combined with a bispecific antibody, and that allows us to see how we can change the treatment paradigm, if you will, because historically, we've had other agents that have been used, image proteasome inhibitors, and that has been part of the treatment paradigm.

Here we were looking at leveraging a Phase III study where we're combining these two powerful immunotherapies together that are so efficacious independently, but now bringing them together without having any of the classical treatment modalities that have been used in the past, having a synergistic effect between the two of them being safe, and you'll hear me say that again and again, because safety is so critical for our patients. Not only having such an incredible efficacy of the 83% risk reduction of progression or death, but also these patients were able to have a three-year period now and continuing where they are do not have to worry about their cancer and that is so profound.

As a practicing Hematologist Oncologist, I can tell you this is something that means so much to me as a practicing physician that we want to be able to offer these kinds of therapies, because this is what changes the potential standard of care for these patients, and offers them an opportunity to have such a powerful combination that can put them not only into remission, but bring them back to that level of normalcy in their life, being able to get back to not worrying about cancer, getting back to the normalcy of their personal and professional lives, that just makes it so compelling, and this is why we really feel that this is something that is going to offer a new standard of care for patients in the second line, plus setting

PE: The approval for the treatment came just 55 days after filing under the FDA Commissioner's National Priority Voucher Pilot Program, making this the first J&J regimen and the first blood cancer therapy to move through that pathway. What does J&J's experience navigating the CNPV program tell us about how the industry should be thinking about this mechanism going forward?
Khan: Johnson, and Johnson has an unwavering commitment to continuing the quest to develop better, new therapies for multiple myeloma. We started this journey over 10 years ago with Darzalex ,we've continued on that journey. We've developed multiple therapies, and really it's about data. You'll see me harken back to the data, because we are data driven.

Seeing 83% reduction, hazard ratio of 0.17, patients living at the 3.3-year mark, being cancer free, the data is really what drove the priority voucher pilot program. That really was a testament to how impeccable this data is and to be awarded that is just been a fantastic. Why is it fantastic? Because it's great for patients.

What I say is that we take great pains in ensuring that the studies that we develop are comprehensive, are well thought out. As we go through the studies we have learned in doing this process is its ensuring that our therapies are safe, and how do we do that? We do it by maintaining efficacy with two things.

Number one, when you combine these two therapies together, we use prophylaxis with a therapy called IVIG, intravenous immunoglobulin that ensures that patients do not develop serious grade infections. That was part of the learning of the study as we move through the study.

Number two, we also ensured that the dosing schedule was the same for Darzalex and Tecvayli. So, by doing that, it also decreased the risk of serious infections for these patients. Those are key things that we wanted to make sure that we did when you're going through a study that has tremendous opportunity. You want to ensure, not only that from an efficacy standpoint, you see such great results, but for a safety standpoint as well.

I think that is the key piece that has helped us really move this study forward for patients and why the FDA award awarded us this priority voucher pilot program, is I can tell you again, I go back to as a Hematologist Oncologist, as a practicing doctor, when I saw these results it's an incredibly emotional moment, because we realized that there's so much hope cancer doctors, we look for hope for our patients. That's what we want. We want to offer hope, real, meaningful hope. There's nothing better than when data shows that not just the majority, but nearly all your patients are getting out to the three-year mark, are living, are cancer free, are getting back to normalcy, are safe. There's nothing better as a physician that I can think of, and the fact that FDA gave us this voucher pilot program is a testament to them understanding the value of this data.

We always say at Johnson and Johnson, while we want to move with speed, because our patients don't have the gift of time, we need to move with speed with great care and accuracy, and by doing that, we ensure that patients are safe, patients are potentially going to see transformation in terms of therapy opportunity which this study offers, and then we're able to move quickly towards a regulatory approval, and the fact that this came 55 days after the filing is a testament to that