A Faster Tandem CAR T-Cell Product, Zamto-Cel Being Studied in DLBCL | Nirav Shah, MD, MSHP | #ASH24

Hi, my name is Nirav Shah. I'm an associate professor from the Medical College of Wisconsin in Milwaukee, excited to be here at ASH 2024 and share some of the work we're doing in relapsed refractory diffused large B-cell lymphoma. So patients who have relapsed refractory diffused large B-cell lymphoma, a treatment modality that's used often is something called CAR T-cell therapy. This is sort of becoming a well-established treatment for patients with relapsed disease, and most CARs currently available target one protein on the B-cell called CD19. While that therapy is effective, still most patients will eventually relapse with diffused large B-cell lymphoma, suggesting that newer treatment modalities are needed. At the Medical College of Wisconsin, we've worked with collaborators to help develop a tandem dual targeted CAR. So this CAR T-cell product doesn't only target CD19, it targets a second protein called CD20, with the goal being that targeting more than one protein can lead to better outcomes. Additionally, we're doing something different in manufacturing by using a closed automated device called the Clinamax Prodigy that allows for rapid, reliable manufacturing, and unlike all the other CAR T-cells out there, can facilitate a fresh infusion of CAR T. Currently, the CAR T's on market, they're frozen, and then they're thawed and re-administered. Data from the Medical College suggested that a fresh product may be more viable and lead to better outcomes. So this early data led to this Daily 2 clinical trial, which is a multi-center clinical trial enrolling patients across the country in relapse for factory diffused large B-cell lymphoma as a third line treatment. We're reporting interim results as part of a pre-planned analysis after 59 valuable patients were treated. These patients with DLBCL were generally in their 60s, had failed at least two lines of prior therapy, and most of them had high-risk disease, high LDH, high prognostic risk factors. And so we're dealing with a sicker group of patients. These patients were then given this fresh CAR T-cell product called Zamptocaptogen, auto-lose cell, as a single infusion. The T-cells were harvested from the patients, sent fresh to a central manufacturing facility. And in order to facilitate that fresh infusion, we started lympho depletion during the manufacturing process. And then when the cells were ready, they were delivered and administered to the patients. What this means for a patient is a true vein-to-vein time of 14 days. And so that's quick, and that's what you want with the CAR T-cell therapy. In terms of clinical outcomes, we're very excited. We had an overall response rate of about 73%, and 51% had a complete remission. In terms of durability, we need longer follow-up, but we had a six-month progression-free survival, meaning the number of patients both alive and still in response of 55%. We need to keep following. We need to get one- and two-year data. This trial is actively accruing, and in fact, we're opening cohorts in diseases like mantle cell lymphoma, CNS lymphoma, and Richter's transformation based on the data we have, and this paradigm-shifting model of rapid manufacturing and a fresh infusion. One question that patients always ask, though, is this is different to new, and you're targeting more than one protein. Is it safe? And what I can share with you now that we've treated this 59 patients is that the safety was impeccable. No patient had high-grade cytokine release syndrome, so grade three or higher. All of it was low-grade and manageable, and only 4% of patients had grade three or higher eye cancer neurotoxicity, again, and that was mostly manageable with treatment. So in conclusion, we've demonstrated a different way to give a novel CAR T with tandem targeting of two proteins, and we have now early data that is both safe and efficacious and that this manufacturing model is feasible because we were able to deliver cells across the country and still give it as a fresh infusion. So we're planning to continue accrual to this trial and report at a future meeting the full results and longer follow-up, of course, to see how these patients do over time, but we're very excited. We appreciate the opportunity to share this work, and if patients have questions, they can always reach out to us because we're continuing to enroll and learn more about this drug product. So clinicaltrials.gov, if you look at our abstract, there's a clinicaltrials.gov number, and that is a national website, and from that website, you can find all the centers across the United States, and the good news is, it's truly a multi-center trial. So wherever you live, there hopefully will be a center within striking distance because we have centers on the West Coast, I'm in the Midwest, East Coast, and southern parts of the country as well, and actually Canada additionally. So I would go to that website and then obviously talk with your doctor and try to find a location. The principal investigator, and I'm Dr. Shah, so my name's listed and our contact information is there too, and we always want to help patients get to a trial opportunity if they feel, and if their doctor feels it's the right opportunity for their situation.