FDA Approval of Subcutaneous Nivolumab CheckMate-67T - Subcutaneous Nivo vs. Intravenous (IV) Nivo

Intro Welcome back to Oncology Brothers podcast. I'm Rohit Ghosain here along with my brother and Co host Rahul Ghosain. Today we are going to focus on recent approval of subcutaneous nibolimab based off of Checkmate 6070 study. Nibolimab were first approved back in 2014 for Melanoma and since then we have utilized immunotherapy in mainly all disease sites. Can we carry out this sub Q indication for all clinical settings, any new safety signals or side effects and importantly, the time toxicity, which is the time saved for these patients? We're going to touch on all this and more with my friend, colleague from my home institution, Roswell Park Comprehensive Cancer Center, Dr. Savi. George Savi, thanks for joining us. Speaker 2 Thank you, Brohit Rahul, happy to be here. Speaker 3 Sabi welcome. I feel a little outnumbered here by the Roswell team and Bill's Mafia, but let's bring the focus back on Checkmate 670. Checkmate 6070 Study Sabi, can you walk us through the study design and its findings? Speaker 2 Yeah. This was a rather large phase three trial designed to show known inferior between the subcutaneously administered new formulation of Nivolmab and the old version IV Nivolmab. Basically this was known inferior trial done in the setting of refractory kidney cancer population. Patients who had one or two prior therapies and no prior immunotherapy were enrolled in this trial. They were randomized in a one to one fashion to receive subcutaneous nuvolumab or IV nuvolumab. The subcutaneous nuvolumab was administered every four weeks and this formulation the mix of nivolumab along with RHU PH20 which allows for large volumes of you know drug to be administered subcutaneously. And then the stratification was done using IMDC risk grouping and baseline weight because this was a flat dose opposed to IV was given, you know, 3 Meg per kilogram which was the original approved dose from 2015. The treatment continued until progression unacceptable toxicity, withdrawal of consent, death or completion of two years. Co primary endpoints were time average serum concentration on day 28 and the concern concentration after reaching minimum steady state as secondary endpoint was, you know powered secondary endpoint for non inferiority testing was objective response rate by a blinded independent central review. So this was the design of the study. The Co primary endpoints were basically assessing the concentration of you know, both the sub Q versus IV nubile and making sure that you know this this falls within the non inferiority range. This happened to be a larger trial because there was a secondary endpoint of objective response rate. So that's why this trial is nearly 500 patient trial. Otherwise it could have been less 100 patients to achieve the the PK endpoints alone. Speaker 1 Thanks so much for going over that, Savvy. As you mentioned, this was a known inferiority study looking at pharmacokinetics, efficacy and safety. Can we switch to subcutaneous formulation? Based on the results, all endpoints were met, but SABI in our clinical practice, can we now substitute subcu formulation for all patients wherever IV was used as a single agent, the. Speaker 2 Approval is wherever nivolumab is applicable in 21. I think 21 is for different indications. Can you switch everybody to subcu? You may, but in a patient receiving nivolumab in combination with another IV drug like chemotherapy or ibilumab, it doesn't make much sense to give some drugs IV and one is subcutaneously. So that becomes more tedious unless it's all given in the same place. But definitely you can transition single agent involve. Our patients if they're getting early involve of infusion, they may transition to sub Q, which makes sense. They save a lot of time avoiding the infusion chair wait time and all those prime times and all those things. Ideally, a subcutaneously administered nivolumab can be given in the doctor's office or the clinic itself. This awards need for going to the infusion center if that's separate from the clinic. So that makes it easy for the patients. They won't have to make an additional appointment for the infusion chair and they won't have additional check in, wait time, check out, etcetera. At the infusion center. They'd end up saving one to two hours. Even though infusion time is 30 to 60 minutes for intravenous nivolumab, they end up saving, you know, one to two hours every time they receive nivolumab. The important thing is this, most of the patients will receive annual amendment. Such drugs have advanced cancer and they have a, you know, they have limited time. In most cases, you know, they have limited time. It makes sense to give the time back to the patient rather than having them hang out in hospitals and clinics for more time. Speaker 3 And wrote then as you alluded to initially, nivolumab since its approval for Melanoma in 2014 is approved for multiple disease sites, right, for multiple different indications, new adjuvant lung cancer, metastatic RCC, upper GI malignancies list 3 to 5. Sub Q injection is not only precious for patients because they'll be spending less time in the infusion center, but it's also important for us because as treating physicians, we have pressure to get more patients in the infusion center in a timely manner. So this is exciting. But coming back to this Saby, when we're giving subcutaneous injection, we have to worry about site related reactions. How frequently did we see this with nivolumab? How much volume are we giving with sub Q injection? Speaker 2 In terms of the volume the subcutaneous submits, cernivolumab has nearly 10ML. The RHU PH20 allows for the 10ML injection to be done subcutaneously over 3 to 5 minutes. RHU PH20 is a reversible degrader of the subcutaneous connective tissue which allows for depot type injections. Once it's absorbed it will get back to normal. So that's the volume. In terms of local reactions, you know, the subcupations had, you know, some local reactions which were low grade sounds limiting and did not really require much intervention. But in, in terms of percentage any grade, there were like 8% of patients who had local side reactions and there were no grade 3 or 4 events in terms of local reactions, all of them were self limiting and they went away with conservative management. So it's not like a chemotherapy leakage or anything. This is very safe. Speaker 1 And in terms of the beyond local reactions, any other side effects that we have to keep in mind with sub Q formulations that are slightly different than IV? Speaker 2 Not really. You know, when you look at this common adverse events listed in this table here, you can see that the adverse events from sub Q are similar to that of IV, if not a little lower frequency, but it's not inferior. I wouldn't say that this is superior, but it's very similar to the IV formulation and similar type of toxicity, arthritis of fatigue, etcetera and immediate adverse events or were similar. So the same drug causing same type of effect and same type of side effect. So there was no, no much, you know, safety concerns from the sub Q compared to the IV drug? Speaker 1 OK. How is your practice different post disapproval? And now how is your practice different post disapproval? Are you going to be utilizing this is going to be your go to wherever nabilimab at least for maintenance therapy or singly where it's being utilized? Speaker 2 So we started the discussion with our leadership at the hospital to switch the world map to sub Q. If you open up more infusion chairs by transitioning patients to outpatient clinics, we might be able to treat more patients because the wait time to a chair will reduce significantly with this. So we had done a calculation with the help of our infusion leadership at the institute. I found out that your free transition only the single agent administered in the world maps to sub Q. You know we will save on an average 20 hours or more of chair time every week. Speaker 3 Wow. Speaker 2 So that's that's that's a lot, which means we can have 20 hours of chair time opened up for other treatments. It's a win, win situation for all patient, not just patients receiving the world map, all the patients who are waiting for infusion also. So that's how I see it. Speaker 3 And again, you said that was just for monotherapy, not for combination with chemotherapy and so forth. Speaker 2 Actually for combination our numbers are double. So it will be basically 40 hours of time saved. But it doesn't necessarily mean that say for example, if a patient is receiving nivolumab and cabocentinib, you know, patient is taking the Cabo centinib at home, they're getting single agent nivolumab in the infusion center. So that's an ideal patient. And patients who are on AP NIBO regimen after finishing four cycles of AP with the NIBO, they can be transitioned. Pretty much all the patients are receiving adjuvant NIBOLA MAP or single agent NIBOLA MAP, They're all ideal for, for this. You know, in any indication, that's how the approval was. This was for, you know, all indication were, you know, the world MAP is approved. Speaker 1 Right. As you stated, Sabi, based on the time saving here, that is 20 to 40 hours and this is within a week time. That's huge and that is the biggest win here. Sabi, any first hand experiences around this from patient perspective that you had because you were actively involved with the trial and the first author that you came across from the patients and their families? First-hand experiences from patients Yes. I have treated many patients on the trial with the sub Q and IV nivolumab and patients basically loved it. There was no reaction for which I was called to see the patient in the infusion center or the Research Center. As a matter of fact, I have a lot of patients who are on long term new world map treatment. A lot of them when they saw the news about my presentation, they were asking when is it available, doctor, when can we have the sub Q and avoid the whole infusion center visit and all those things. So patients are excited about it. As far as I know. That's my experience. Patient advocacy groups have also expressed a similar kind of reaction from patients from all over the world. This will be a win win situation for patients and the treating physician and team. Speaker 3 We were having similar discussions in our practice with the University of Rochester. We now also have a Tisalus map in subcu formulation, but the adoption has been low because of the insurance and the uphill battle to get this approved by the peers. But as you're pointing this out, you're saving more time, you're treating more patients. It's better quality of life for our patients. This is something that we all need to get creative and make more available for our patients. I hope that the path for nivolumab is better. Sabe, any final thoughts or advice for our listeners on this recent approval of sub Q nivolumab? Final thoughts Yeah. So in the US, we were talking about the practice in the US and it will definitely give back time to the patients and reduce the time spent at the Cancer Center or the clinics. And moreover, that's also time toxicity as Rohit alluded to. I'm sorry, toxicity can be reduced, especially patients rather have their time with the family and not in the hallways of a hospital, number one. Number two, in a lot of places. This trial was done in 17 countries in a lot of places where you know, access to large centers are are difficult for some patients. This will make it easy for patients to receive treatments close to close to home in clinics rather than going to large infusion Centers for doctors coming to the to the community or something like that. So that's another advantage. And of course, Rahul, as you mentioned, adoption was low with T cell, but I don't think as many indications. So maybe it might be different because of the sheer volume used. You know, I just mentioned our volumes at at the Castle at Russell Park. And I mean there are a lot larger centers. So we're not the largest center when you consider the impact of large centers adopting this, you know, I think impact will be very significant and our patients will will really I guess will feel the difference and time saved in terms of course, I don't think I'm in any position to comment on this, but I'm hoping that, you know, the the manufacturer BMS will work with the work with the payers in terms of pricing appropriately so that everybody can access it and get the benefits of time saved while receiving a life for longing drug like nivolumab. Speaker 3 Absolutely. Thank you Doctor Savi George for sharing your insights with us today around Sub Q formulation of nivolumab, which was approved on December 27th, 2024 based off your study Checkmate 670. What does disapproval mean to patients? For our listeners, let us go over a quick recap today with Doctor Savi George from Roswell Park Comprehensive Cancer Center. We had a chance to discuss the recent approval of subcutaneous nivolumab based off Checkmate 670 ROHAT. What does disapproval really mean to you? To our patients, Importantly for us in the community. Speaker 1 Rahul, big take home points from me here are we can carry over the subcutaneous formulation in all mono therapy indications as Doctor George mentioned that is for maintenance aspect or when combining with drugs like cabozantinib or oral therapies. This is a win win for our patients because less time in infusion center, three to five minute injection and you're done. Speaker 3 Yeah, I have to agree. This is great. But importantly we're also not compromising any outcomes. This is a non inferior study and all primary endpoints of pharmacokinetics, safety, data and efficacy were met. And this is all with better quality of life. I'm walking away with a plan to use this in all settings as long as I can get this approved by insurance for our listeners, as always, thanks for joining us. Make sure to check out our other FDA drug approval discussions, conference highlights and treatment algorithms. We are at the Oncology Brothers.