CheckMate 67T: Subcutaneous Nivolumab Non-Inferior to Intravenous in Advanced RCC - Laurence Albiges
November 1, 2024
Laurence Albiges joins Zachary Klaassen to discuss the CheckMate 67T trial results. The phase 3 non-inferiority study compares subcutaneous versus intravenous administration of nivolumab in renal cell carcinoma patients who have failed prior VEGF-TKI therapy. The trial meets its co-primary pharmacokinetic endpoints, demonstrating non-inferiority of subcutaneous administration, while showing similar progression-free survival and response rates between the two delivery methods. The conversation highlights the practical advantages of subcutaneous administration, including reduced hospital time for patients (5 minutes versus 30-60 minutes for IV) and improved healthcare resource utilization. Dr. Albiges emphasizes the significance of this development in the context of long-term immunotherapy treatment across multiple cancer types, with subcutaneous delivery offering greater convenience for both patients and healthcare systems without compromising safety or efficacy.
Biographies:
Laurence Albiges, MD, PhD, Medical Oncologist, Gustave Roussy Cancer Campus, University of Paris Sud, Paris, France
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
Biographies:
Laurence Albiges, MD, PhD, Medical Oncologist, Gustave Roussy Cancer Campus, University of Paris Sud, Paris, France
Zachary Klaassen, MD, MSc, Urologic Oncologist, Assistant Professor Surgery/Urology at the Medical College of Georgia at Augusta University, Wellstar MCG, Georgia Cancer Center, Augusta, GA
Related Content:
ESMO 2024: Subcutaneous Nivolumab vs Intravenous Nivolumab in Patients with Previously Treated Advanced or Metastatic Clear Cell Renal Cell Carcinoma: Updated Efficacy and Safety Results from CheckMate 67T
CaboPoint Trial: Cabozantinib in Second-Line RCC Treatment - Laurence Albiges
EAU 2024: Moving Towards Intensified Treatment Paradigms in First Line Metastatic Kidney Cancer: Triplet Combinations at Any Cost - Is More Always Better? Yes, the More the Merrier
ESMO 2024: Subcutaneous Nivolumab vs Intravenous Nivolumab in Patients with Previously Treated Advanced or Metastatic Clear Cell Renal Cell Carcinoma: Updated Efficacy and Safety Results from CheckMate 67T
CaboPoint Trial: Cabozantinib in Second-Line RCC Treatment - Laurence Albiges
EAU 2024: Moving Towards Intensified Treatment Paradigms in First Line Metastatic Kidney Cancer: Triplet Combinations at Any Cost - Is More Always Better? Yes, the More the Merrier
Read the Full Video Transcript
Zachary Klaassen: Hi, my name is Zach Klaassen. I'm a urological oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm delighted to be joined today by Professor Laurence Albiges from Gustave Roussy in Paris, France, medical oncologist. Laurence, thanks very much for joining us today.
Laurence Albiges: Thank you very much for having me.
Zachary Klaassen: So we're going to talk about some exciting ESMO data you presented, specifically CheckMate 67T. And so this is looking at a subcutaneous versus an IV infusion of nivolumab. So maybe just take our listeners through some of the background, and I'd love for you to share your trial design and the key results.
Laurence Albiges: Sure, with pleasure. So the big picture is the following. Over the course of the past few years, the field has changed with regard to the use of subcu administration in oncology. And we knew that from heme-oncology, breast cancer, and it's coming slowly with regard to immune checkpoint inhibitor subcu administration with one prior study with atezolizumab.
And what is the interest of that? I think the big picture is that it has an interest both from the patient perspective to avoid the need for IV venous ports, but also a little more flexibility and so on. And also the care team because of how you organize your infusion rooms and make sure that your patients spend as little time as possible in the hospital. And so I think it really makes sense to try to move the field forward with regard to subcu instead of IV administration.
So the 67T is a nivolumab subcu versus IV study. It's a non-inferiority phase 3 that was designed for patients that are treated with RCC and that are using nivolumab as a single agent, meaning you have to have failure of prior VEGF-TKI. And because it's about the route of administration, the primary endpoint had to be PK. So it's a co-primary PK endpoint for non-inferiority, looking at two different parameters that are the average concentration but also the residual concentration. But as a physician, I also wanted to have a clinically meaningful endpoint. So it was also powered for response rate and closely looking also at PFS and ultimately overall survival.
So to put a long story short, about 500 patients have been randomized to receive nivolumab, subcu versus nivolumab IV, and IV was every two weeks because it was initially developed this way at 3 milligrams per kg, while subcu is administered every four weeks. And so the study met its co-primary endpoint, which was to demonstrate the PK non-inferiority of nivolumab administered subcu versus IV. And if you pay attention to the numbers, actually the level of exposure seems to be higher with the subcu administration when compared to the IV administration.
Now getting to the clinical endpoint, the study showed also a very similar progression-free survival, numerically higher with the subcu administration, 6.34 versus 5.65 for IV. So clearly not underexposing our patients and having similar clinical benefit for PFS, but also for response rates. With more follow-up, we're now with 15 months follow-up, we have 26.6% objective response rate by independent review for the subcu versus about 20.6% for the IV. So we are clearly seeing a similar efficacy in terms of subcu versus IV, bearing in mind that the treatment administration is five minutes versus 30 up to 60 minutes depending on the centers.
So what about safety? Well, it's important to stress that we didn't see any increased safety issues related to immune reaction with the subcu administration. Of course, because this is local injection, we do have some local site reactions, but all of them are grade one to two and fully recovered. So I think in terms of safety, it's also very consistent. No added toxicity, no new signal.
So overall I think that the study design, because it's a non-inferiority trial, clearly established PK as non-inferior to IV administration, similar efficacy, similar safety. And it does have an impact to me in terms of convenience, both from the patient perspective, but also our healthcare system. And that is the reason why it was published as a concomitant publication in Annals of Oncology during this ESMO 2024.
Zachary Klaassen: Laurence, thanks very much for sharing that data. I think the non-inferiority is a perfect design for this, and I think to power it to PK, we want to make sure it's working first before we look at efficacy and other endpoints. I guess when you talk to your patients about this, so sitting in the clinic, what do they tell you in terms of convenience? Do they like it? I mean, obviously you mentioned five minutes versus up to an hour. What's sort of your feedback from the patient standpoint?
Laurence Albiges: I mean, it's important to stress here, to answer your question, that IO is now being used in so many settings, so many tumor types. And just if you think about nivolumab, you have data in the adjuvant space in some other disease type. RCC, we have maintenance nivolumab, after nivolumab, you can even have first line. So it's a lot of patients are being exposed to this agent and it's also a treatment in the long run. It could be one year, two years. So for the patient, the time they spend in a hospital is something they have in their minds. And the shorter we can bring that is important. Of course, the IV route, for some patients, is something they're not 100% comfortable with and we understand that. So they're happy to have more convenient administration. And it's not dedicated to RCC, it's not specific to IO, but I'm glad the IO field is moving this way.
Zachary Klaassen: Yeah, that's great. And from a healthcare utilization standpoint, if somebody's setting up their pharmacy or their infusion clinic, it's almost like coming in for a Lupron injection, it's quick for prostate cancer. How do you see this benefiting just resource utilization, as we start to implement this in the clinic?
Laurence Albiges: It's obvious that worldwide, we have a shortage of staff for our activities and so the time we have is reduced, so we need to have efficient processes. And it's not the same to have to schedule one hour IV in our infusion room than have to have a walk-in, walk-out, subcu dedicated seat basically. And the patient can show up and have the subcu whenever he or she's coming into the clinic to have this treatment. So I think it gives flexibility in the day for the patient, but also in terms of preparation for your pharmacy. So this is very important to have in mind.
Zachary Klaassen: Yeah, great points. Awesome discussion. I'd like you just to give maybe two or three take-home messages for our listeners today.
Laurence Albiges: The take-home messages to me are that we are moving towards subcu administration for immune checkpoint inhibitor. This study demonstrated the non-inferiority on PK, but also consistent activity and safety. So to me, this is a potentially practice-changing trial.
Zachary Klaassen: Wonderful. Professor Albiges, thanks so much for sharing your insight on CheckMate 67T, thank you.
Laurence Albiges: Thank you.
Zachary Klaassen: Hi, my name is Zach Klaassen. I'm a urological oncologist at the Georgia Cancer Center in Augusta, Georgia. I'm delighted to be joined today by Professor Laurence Albiges from Gustave Roussy in Paris, France, medical oncologist. Laurence, thanks very much for joining us today.
Laurence Albiges: Thank you very much for having me.
Zachary Klaassen: So we're going to talk about some exciting ESMO data you presented, specifically CheckMate 67T. And so this is looking at a subcutaneous versus an IV infusion of nivolumab. So maybe just take our listeners through some of the background, and I'd love for you to share your trial design and the key results.
Laurence Albiges: Sure, with pleasure. So the big picture is the following. Over the course of the past few years, the field has changed with regard to the use of subcu administration in oncology. And we knew that from heme-oncology, breast cancer, and it's coming slowly with regard to immune checkpoint inhibitor subcu administration with one prior study with atezolizumab.
And what is the interest of that? I think the big picture is that it has an interest both from the patient perspective to avoid the need for IV venous ports, but also a little more flexibility and so on. And also the care team because of how you organize your infusion rooms and make sure that your patients spend as little time as possible in the hospital. And so I think it really makes sense to try to move the field forward with regard to subcu instead of IV administration.
So the 67T is a nivolumab subcu versus IV study. It's a non-inferiority phase 3 that was designed for patients that are treated with RCC and that are using nivolumab as a single agent, meaning you have to have failure of prior VEGF-TKI. And because it's about the route of administration, the primary endpoint had to be PK. So it's a co-primary PK endpoint for non-inferiority, looking at two different parameters that are the average concentration but also the residual concentration. But as a physician, I also wanted to have a clinically meaningful endpoint. So it was also powered for response rate and closely looking also at PFS and ultimately overall survival.
So to put a long story short, about 500 patients have been randomized to receive nivolumab, subcu versus nivolumab IV, and IV was every two weeks because it was initially developed this way at 3 milligrams per kg, while subcu is administered every four weeks. And so the study met its co-primary endpoint, which was to demonstrate the PK non-inferiority of nivolumab administered subcu versus IV. And if you pay attention to the numbers, actually the level of exposure seems to be higher with the subcu administration when compared to the IV administration.
Now getting to the clinical endpoint, the study showed also a very similar progression-free survival, numerically higher with the subcu administration, 6.34 versus 5.65 for IV. So clearly not underexposing our patients and having similar clinical benefit for PFS, but also for response rates. With more follow-up, we're now with 15 months follow-up, we have 26.6% objective response rate by independent review for the subcu versus about 20.6% for the IV. So we are clearly seeing a similar efficacy in terms of subcu versus IV, bearing in mind that the treatment administration is five minutes versus 30 up to 60 minutes depending on the centers.
So what about safety? Well, it's important to stress that we didn't see any increased safety issues related to immune reaction with the subcu administration. Of course, because this is local injection, we do have some local site reactions, but all of them are grade one to two and fully recovered. So I think in terms of safety, it's also very consistent. No added toxicity, no new signal.
So overall I think that the study design, because it's a non-inferiority trial, clearly established PK as non-inferior to IV administration, similar efficacy, similar safety. And it does have an impact to me in terms of convenience, both from the patient perspective, but also our healthcare system. And that is the reason why it was published as a concomitant publication in Annals of Oncology during this ESMO 2024.
Zachary Klaassen: Laurence, thanks very much for sharing that data. I think the non-inferiority is a perfect design for this, and I think to power it to PK, we want to make sure it's working first before we look at efficacy and other endpoints. I guess when you talk to your patients about this, so sitting in the clinic, what do they tell you in terms of convenience? Do they like it? I mean, obviously you mentioned five minutes versus up to an hour. What's sort of your feedback from the patient standpoint?
Laurence Albiges: I mean, it's important to stress here, to answer your question, that IO is now being used in so many settings, so many tumor types. And just if you think about nivolumab, you have data in the adjuvant space in some other disease type. RCC, we have maintenance nivolumab, after nivolumab, you can even have first line. So it's a lot of patients are being exposed to this agent and it's also a treatment in the long run. It could be one year, two years. So for the patient, the time they spend in a hospital is something they have in their minds. And the shorter we can bring that is important. Of course, the IV route, for some patients, is something they're not 100% comfortable with and we understand that. So they're happy to have more convenient administration. And it's not dedicated to RCC, it's not specific to IO, but I'm glad the IO field is moving this way.
Zachary Klaassen: Yeah, that's great. And from a healthcare utilization standpoint, if somebody's setting up their pharmacy or their infusion clinic, it's almost like coming in for a Lupron injection, it's quick for prostate cancer. How do you see this benefiting just resource utilization, as we start to implement this in the clinic?
Laurence Albiges: It's obvious that worldwide, we have a shortage of staff for our activities and so the time we have is reduced, so we need to have efficient processes. And it's not the same to have to schedule one hour IV in our infusion room than have to have a walk-in, walk-out, subcu dedicated seat basically. And the patient can show up and have the subcu whenever he or she's coming into the clinic to have this treatment. So I think it gives flexibility in the day for the patient, but also in terms of preparation for your pharmacy. So this is very important to have in mind.
Zachary Klaassen: Yeah, great points. Awesome discussion. I'd like you just to give maybe two or three take-home messages for our listeners today.
Laurence Albiges: The take-home messages to me are that we are moving towards subcu administration for immune checkpoint inhibitor. This study demonstrated the non-inferiority on PK, but also consistent activity and safety. So to me, this is a potentially practice-changing trial.
Zachary Klaassen: Wonderful. Professor Albiges, thanks so much for sharing your insight on CheckMate 67T, thank you.
Laurence Albiges: Thank you.