CheckMate-67T: Subcutaneous Nivolumab Shows Comparable Results to IV, Reduces Treatment Burden in RCC - Saby George
March 5, 2024
Dan George discusses the CheckMate-67T study with Saby George, a phase three trial comparing intravenous and subcutaneous administration of nivolumab in treatment-refractory kidney cancer patients. Conducted across 73 centers in 17 countries, this trial aimed to assess if subcutaneous nivolumab could match the systemic effects of its IV counterpart. Meeting its co-primary pharmacokinetic endpoints and showing a non-inferior objective response rate, the study suggests subcutaneous administration as an effective, patient-friendly alternative. With similar efficacy and side effects between the two forms, this approach could significantly reduce treatment burdens, promising broader application across nivolumab's indications and potentially transforming patient care practices.
Biographies:
Saby George, MD, FACP, Associate Professor, Roswell Park Comprehensive Cancer Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY
Daniel George, MD, Medical Oncologist, Professor, Departments of Medicine and Surgery, Duke Cancer Institute, Duke University, Durham, NC
Biographies:
Saby George, MD, FACP, Associate Professor, Roswell Park Comprehensive Cancer Center, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY
Daniel George, MD, Medical Oncologist, Professor, Departments of Medicine and Surgery, Duke Cancer Institute, Duke University, Durham, NC
Related Content:
ASCO GU 2024: Subcutaneous Nivolumab Versus Intravenous Nivolumab in Patients With Previously Treated Advanced or Metastatic Clear Cell Renal Cell Carcinoma: Pharmacokinetics, Efficacy, and Safety Results From CheckMate 67T
Phase 3 CheckMate -67T Trial of Subcutaneous Nivolumab (nivolumab and hyaluronidase) Meets Co-Primary Endpoints in Advanced or Metastatic Clear Cell Renal Cell Carcinoma
ASCO GU 2024: Subcutaneous Nivolumab Versus Intravenous Nivolumab in Patients With Previously Treated Advanced or Metastatic Clear Cell Renal Cell Carcinoma: Pharmacokinetics, Efficacy, and Safety Results From CheckMate 67T
Phase 3 CheckMate -67T Trial of Subcutaneous Nivolumab (nivolumab and hyaluronidase) Meets Co-Primary Endpoints in Advanced or Metastatic Clear Cell Renal Cell Carcinoma
Read the Full Video Transcript
Daniel George: Hi. I'm Dr. Dan George from Duke University. It's my pleasure on behalf of UroToday here at GU ASCO '24 to have a conversation with my good friend and colleague, Dr. Saby George, from Roswell Park, on his really, I think, seminal now phase three study results that he just presented at our national meeting on the comparison of IV nivolumab versus subcu nivolumab in the CheckMate-67T study.
Dr. George, walk us through a little bit. This study, what was the purpose and goal, and what was the design?
Saby George: Thank you, Dr. George, and UroToday for the opportunity. The study, CheckMate-67T, is a randomized, open-label phase three trial of subcutaneous nivolumab compared to intravenously administered nivolumab. This was tested in treatment-refractory kidney cancer patients who had up to one to two prior lines of therapy. The co-primary endpoint was C average day 28 and C minimum steady state PK endpoints.
Daniel George: Pharmacokinetic endpoints. We're looking at the drug exposure.
Saby George: Exactly.
Daniel George: And are these equivalent forms?
Saby George: Exactly, trying to see if a subcutaneous administration of nivolumab gets into the systemic circulation enough to have the effect like the IV drug. That's basically the goal. The key secondary powered endpoint was objective response rate by blinded independent center review. Those were the primary and secondary endpoints of the study.
Daniel George: Okay.
Saby George: The study was conducted in 73 centers across 17 different countries.
Daniel George: It's a big multinational phase three study.
Saby George: Absolutely. Absolutely. The treatment included in arm A was subcutaneously administered nivolumab, along with rHuPH20, which was given every four weeks.
Daniel George: Now rHuPH-
Saby George: rHuPH20.
Daniel George: What is that?
Saby George: So rHuPH20 is a reversible degrader of hyaluronic acid.
Daniel George: Okay.
Saby George: Seen in the extracellular matrix, which allows for larger volumes of co-formulated agent to be administered. In this case, nivolumab.
Daniel George: How big a volume was that?
Saby George: The volume for 1200 milligrams of nivolumab was approximately 10 ml.
Daniel George: Okay. That was administered once every four weeks?
Saby George: Every four weeks.
Daniel George: As a subcu injection. So, this is something our nurses do. It's research, but even on a clinical level, this would not be a home injection. This is something we'd be doing in the clinic.
Saby George: That's right.
Daniel George: And how long does that injection take?
Saby George: The injection takes approximately five minutes or less.
Daniel George: Okay. A big change versus an IV infusion requiring an IV and then administration, slow infusion over 30 minutes or whatnot?
Saby George: Absolutely. Yeah. The comparison was IV administered nivolumab, which was approved in 2015 based on the CheckMate-025 study.
Daniel George: What did you find? This was what you said, 500 patients or so almost?
Saby George: 495 patients were randomized.
Daniel George: Okay.
Saby George: And the study met its co-primary endpoints, C average day 28, and C minimum steady state for non-inferiority.
Daniel George: Okay. We saw essentially similar results between-
Saby George: Absolutely, absolutely.
Daniel George: Okay. And what about on an efficacy level?
Saby George: On the efficacy level, the key powered secondary endpoint was the objective response rate by blinded independent central review, which also met its non-inferiority threshold.
Daniel George: What were those numbers? What did that look like?
Saby George: The response rate from the subcu was 24.2%, and the IV was 18.2%.
Daniel George: So, numerically higher, but similar?
Saby George: Numerically higher, but we call it non-inferiority because that's how it was powered.
Daniel George: Were there any other efficacy endpoints that you looked at?
Saby George: Yes, of course. Other secondary endpoints included progression-free survival. The progression-free survival from the subcu arm was 7.23 months compared to 5.65 months from the IV arm.
Daniel George: So again, numerically higher, but non-inferior?
Saby George: Numerically higher. We can't say that it's better.
Daniel George: Okay. Right. This is a secondary endpoint.
Saby George: Yeah.
Daniel George: Got it. Got it. Okay. And then lastly, side effects. Were there differences in the toxicity profiles?
Saby George: Yes, the side effects were very similar between the two arms. And again, it's consistent across both arms, subcu and IV arms, similar side effects, similar percentages, and similar discontinuation rates, etc.
Daniel George: Steroid use, all that. Very similar.
Saby George: All that. Very similar.
Daniel George: Okay. Bring us home here. What does this mean for the field now for those of us... Is this going to lead to potential FDA approval of this new formulation of nivolumab, and how do you see that being implemented out there in practice?
Saby George: It's expected that the FDA will grant approval based on these results, and this is a game changer. I think it's practice-changing trial data showing that subcutaneously administered nivolumab is at least as good as the intravenously administered nivolumab. And this is huge in terms of reducing the treatment burden on patients. Various studies have shown that patients prefer subcutaneously administered treatment over IV.
Daniel George: Oh, absolutely. I mean, I can think of my patients who just have trouble with IV access needing ports, and these are therapies patients can take for months, sometimes years.
Saby George: Yeah.
Daniel George: And having to avoid the complications and risks associated with a port or over and over again IVs. That alone is significant. Then there's also the burden of the time in the chairs and the growing limitations we have on our treatment centers for access to these therapies. So, having a therapy that can be given over minutes instead of half an hour or so, over the course of a year, that's hours and hours of therapy that you've saved the patient in terms of time in the chair, right?
Saby George: Absolutely. I did look at numbers from our center in terms of how many nivolumabs we use every year.
Daniel George: Yeah.
Saby George: We use roughly 2000 doses of nivolumab every year—
Daniel George: Wow.
Saby George: —in combination with other drugs or as a single agent.
Daniel George: Right.
Saby George: As a single agent nivolumab, the use is roughly 900 doses a year.
Daniel George: Right.
Saby George: If we divide it over the year, I mean, every week we could save close to 20 hours of chair time by transitioning from IV to subcu given in the clinic. And more than that, having an infusion appointment, we don't need to make that appointment. They can just have it in the clinic and go home. And that cuts the duration of time they spend in the clinic from roughly four to five hours down to two hours.
Daniel George: Yeah. Just keep the car running.
Saby George: Absolutely.
Daniel George: No. Well, but I think this is really kudos to the company and to you for doing what I would really consider a patient-centric study, a formulation that I think can really unburden both our centers and the patients. And I think something that, you tell me, but can this be applied more broadly than the indication it was tested in?
Saby George: I bet this can be applied more broadly because the primary co-primary endpoints were PK. As you know, nivolumab is approved for 22 different indications across multiple malignancies, and if subcutaneously administered nivolumab can perform the same way as the intravenously administered nivolumab, it can be applied to all those indications. And so that's for sure; the implications are very broad. And moreover, in addition to saving chair times, the patients out in the country have better access to care. They don't need to go to an infusion center; they can have this given in a clinic. That's another advantage.
Daniel George: Right. Interesting. Yeah. No, and it's the same drug at the end of the day.
Saby George: Yeah.
Daniel George: So you can have confidence in that.
Saby George: Absolutely.
Daniel George: Well, Dr. George, well-done study. Thank you so much for taking your time to join us today at UroToday and share this, what really sounds like a groundbreaking new formulation for this ICI therapy, and really appreciate your time.
Saby George: Thank you, Dr. George, for having me.
Daniel George: Hi. I'm Dr. Dan George from Duke University. It's my pleasure on behalf of UroToday here at GU ASCO '24 to have a conversation with my good friend and colleague, Dr. Saby George, from Roswell Park, on his really, I think, seminal now phase three study results that he just presented at our national meeting on the comparison of IV nivolumab versus subcu nivolumab in the CheckMate-67T study.
Dr. George, walk us through a little bit. This study, what was the purpose and goal, and what was the design?
Saby George: Thank you, Dr. George, and UroToday for the opportunity. The study, CheckMate-67T, is a randomized, open-label phase three trial of subcutaneous nivolumab compared to intravenously administered nivolumab. This was tested in treatment-refractory kidney cancer patients who had up to one to two prior lines of therapy. The co-primary endpoint was C average day 28 and C minimum steady state PK endpoints.
Daniel George: Pharmacokinetic endpoints. We're looking at the drug exposure.
Saby George: Exactly.
Daniel George: And are these equivalent forms?
Saby George: Exactly, trying to see if a subcutaneous administration of nivolumab gets into the systemic circulation enough to have the effect like the IV drug. That's basically the goal. The key secondary powered endpoint was objective response rate by blinded independent center review. Those were the primary and secondary endpoints of the study.
Daniel George: Okay.
Saby George: The study was conducted in 73 centers across 17 different countries.
Daniel George: It's a big multinational phase three study.
Saby George: Absolutely. Absolutely. The treatment included in arm A was subcutaneously administered nivolumab, along with rHuPH20, which was given every four weeks.
Daniel George: Now rHuPH-
Saby George: rHuPH20.
Daniel George: What is that?
Saby George: So rHuPH20 is a reversible degrader of hyaluronic acid.
Daniel George: Okay.
Saby George: Seen in the extracellular matrix, which allows for larger volumes of co-formulated agent to be administered. In this case, nivolumab.
Daniel George: How big a volume was that?
Saby George: The volume for 1200 milligrams of nivolumab was approximately 10 ml.
Daniel George: Okay. That was administered once every four weeks?
Saby George: Every four weeks.
Daniel George: As a subcu injection. So, this is something our nurses do. It's research, but even on a clinical level, this would not be a home injection. This is something we'd be doing in the clinic.
Saby George: That's right.
Daniel George: And how long does that injection take?
Saby George: The injection takes approximately five minutes or less.
Daniel George: Okay. A big change versus an IV infusion requiring an IV and then administration, slow infusion over 30 minutes or whatnot?
Saby George: Absolutely. Yeah. The comparison was IV administered nivolumab, which was approved in 2015 based on the CheckMate-025 study.
Daniel George: What did you find? This was what you said, 500 patients or so almost?
Saby George: 495 patients were randomized.
Daniel George: Okay.
Saby George: And the study met its co-primary endpoints, C average day 28, and C minimum steady state for non-inferiority.
Daniel George: Okay. We saw essentially similar results between-
Saby George: Absolutely, absolutely.
Daniel George: Okay. And what about on an efficacy level?
Saby George: On the efficacy level, the key powered secondary endpoint was the objective response rate by blinded independent central review, which also met its non-inferiority threshold.
Daniel George: What were those numbers? What did that look like?
Saby George: The response rate from the subcu was 24.2%, and the IV was 18.2%.
Daniel George: So, numerically higher, but similar?
Saby George: Numerically higher, but we call it non-inferiority because that's how it was powered.
Daniel George: Were there any other efficacy endpoints that you looked at?
Saby George: Yes, of course. Other secondary endpoints included progression-free survival. The progression-free survival from the subcu arm was 7.23 months compared to 5.65 months from the IV arm.
Daniel George: So again, numerically higher, but non-inferior?
Saby George: Numerically higher. We can't say that it's better.
Daniel George: Okay. Right. This is a secondary endpoint.
Saby George: Yeah.
Daniel George: Got it. Got it. Okay. And then lastly, side effects. Were there differences in the toxicity profiles?
Saby George: Yes, the side effects were very similar between the two arms. And again, it's consistent across both arms, subcu and IV arms, similar side effects, similar percentages, and similar discontinuation rates, etc.
Daniel George: Steroid use, all that. Very similar.
Saby George: All that. Very similar.
Daniel George: Okay. Bring us home here. What does this mean for the field now for those of us... Is this going to lead to potential FDA approval of this new formulation of nivolumab, and how do you see that being implemented out there in practice?
Saby George: It's expected that the FDA will grant approval based on these results, and this is a game changer. I think it's practice-changing trial data showing that subcutaneously administered nivolumab is at least as good as the intravenously administered nivolumab. And this is huge in terms of reducing the treatment burden on patients. Various studies have shown that patients prefer subcutaneously administered treatment over IV.
Daniel George: Oh, absolutely. I mean, I can think of my patients who just have trouble with IV access needing ports, and these are therapies patients can take for months, sometimes years.
Saby George: Yeah.
Daniel George: And having to avoid the complications and risks associated with a port or over and over again IVs. That alone is significant. Then there's also the burden of the time in the chairs and the growing limitations we have on our treatment centers for access to these therapies. So, having a therapy that can be given over minutes instead of half an hour or so, over the course of a year, that's hours and hours of therapy that you've saved the patient in terms of time in the chair, right?
Saby George: Absolutely. I did look at numbers from our center in terms of how many nivolumabs we use every year.
Daniel George: Yeah.
Saby George: We use roughly 2000 doses of nivolumab every year—
Daniel George: Wow.
Saby George: —in combination with other drugs or as a single agent.
Daniel George: Right.
Saby George: As a single agent nivolumab, the use is roughly 900 doses a year.
Daniel George: Right.
Saby George: If we divide it over the year, I mean, every week we could save close to 20 hours of chair time by transitioning from IV to subcu given in the clinic. And more than that, having an infusion appointment, we don't need to make that appointment. They can just have it in the clinic and go home. And that cuts the duration of time they spend in the clinic from roughly four to five hours down to two hours.
Daniel George: Yeah. Just keep the car running.
Saby George: Absolutely.
Daniel George: No. Well, but I think this is really kudos to the company and to you for doing what I would really consider a patient-centric study, a formulation that I think can really unburden both our centers and the patients. And I think something that, you tell me, but can this be applied more broadly than the indication it was tested in?
Saby George: I bet this can be applied more broadly because the primary co-primary endpoints were PK. As you know, nivolumab is approved for 22 different indications across multiple malignancies, and if subcutaneously administered nivolumab can perform the same way as the intravenously administered nivolumab, it can be applied to all those indications. And so that's for sure; the implications are very broad. And moreover, in addition to saving chair times, the patients out in the country have better access to care. They don't need to go to an infusion center; they can have this given in a clinic. That's another advantage.
Daniel George: Right. Interesting. Yeah. No, and it's the same drug at the end of the day.
Saby George: Yeah.
Daniel George: So you can have confidence in that.
Saby George: Absolutely.
Daniel George: Well, Dr. George, well-done study. Thank you so much for taking your time to join us today at UroToday and share this, what really sounds like a groundbreaking new formulation for this ICI therapy, and really appreciate your time.
Saby George: Thank you, Dr. George, for having me.
