Rapcabtagene Autoleucel May Be Safe and Efficacious in R/R DLBCL

Treatment with rapcabtagene autoleucel (YTB323), a next-generation CD19-directed CAR T-cell therapy, demonstrated high, durable responses and favorable safety in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL) in a phase 2 trial (NCT03960840), according to Peter Riedell, MD.

Data from an interim analysis from the phase 2 trial presented at the 2024 ASH Annual Meeting demonstrated that patients treated with rapcabtagene autoleucel (n = 63) achieved an overall response rate (ORR) of 88.3% (95% CI, 77.4%-95.2%).1 Moreover, the complete response (CR) rate was 65.0% (95% CI, 51.6%-76.9%), meeting the primary end point of the study. The median progression-free survival (PFS) and overall survival in all patients was 11.9 months (95% CI, 5.6-not evaluable [NE]) and NE (95% CI, 19.5-NE), respectively.

Notably, rapcabtagene autoleucel was manufactured using the T-Charge platform, which rapidly manufactures CAR T cells in less than 2 days, thereby potentially preserving T-cell stemness.

“Based on the interim analysis in this clinical trial, we saw median vein-to-door time globally of 13 days and 9 days in the United States, which I think compares favorably with what we've seen with some of the commercial products that are available,” Riedell told OncLive® in an interview at the meeting.

In the interview, Riedell explained the rationale for evaluating rapcabtagene autoleucel in this patient population, key efficacy data with the agent, and the next steps for this research.

Riedell is an associate professor of medicine in the Section of Hematology/Oncology, David and Etta Jones Center for Cellular Therapy, at the University of Chicago Medicine in Illinois.

OncLive: What was the rationale for evaluating rapcabtagene autoleucel in relapsed/refractory DLBCL?

Riedell: In DLBCL, CAR T-cell therapy has been heavily utilized and now adopted in the treatment paradigm. However, there are some challenges that exist in operationalizing this therapy. We've seen patients [display disease that is] relapsed/refractory to CAR T-cell therapy based on potential components of the CAR T-cell product, and we've noted that products that are enriched in stem-like T-cells are associated with better proliferation and potentially better persistence.[Addressing] that was one of the aims of adopting this T-Charge platform, which enriches the product in stem-like memory T cells.

The other challenge that we see in the CAR T-cell therapy field is that patients’ diseases often progress while the product is being manufactured. [However], this manufacturing platform harvests T cells after less than 48 hours of culture. That will likely translate into improvements in the turnaround time or the vein-to-door time of this product.

What patient population was enrolled onto this study?

This includes patients with relapsed/refractory DLBCL. Each of these patients had 2 or more prior lines of therapy and needed further treatment. In the context of the trial, the median age was 64 years. This was also a patient population that was heavily pretreated and included high-risk features. The majority of patients received this CAR T-cell product. In the third-line setting, approximately 21% of patients had primary refractory disease, and [25.4%] of patients had double or triple hit phenotype.

What were some of the key efficacy data presented regarding this study?

We saw an ORR of 88.3% in this patient population and the primary end point was best overall response of CR, and that was seen in 65% of patients. If we look at longer-term outcomes, we see that that does translate into a PFS benefit, [with 48.2%] of patients still alive and progression-free at the 12-month mark.

What is the potential impact of the T-Charge platform on the safety, efficacy, and future applications of CAR T-cell therapy in DLBCL?

I think [T-Charge] is an impactful platform to date, and we've seen some encouraging data in terms of the efficacy of this product. It's also a safe product. We saw [any-grade] cytokine release syndrome in [44.4%] of patients and [8%] of patients had any-grade ICANS. But it was, overall, a rare event. There are a lot of attractive features in the context that [rapcabtagene autoleucel is] associated with high efficacy and also seems like a safe product. Therefore, it might certainly have further utilization, should we see some more mature data and further follow-up of these patients.

What are the next steps for this research?

This is a trial that is currently at an interim analysis, so we want to follow up on the patients [still] enrolled onto the study and [better understand the] efficacy and safety we're seeing with this [agent]. This trial is now being conducted with patients in the third-line setting and beyond. Of course, when we have products and constructs that are promising in that setting, we want to move them earlier into the treatment paradigm. This trial also has a separate arm evaluating this construct [for] patients in the frontline setting. In that cohort, patients received 2 cycles of chemotherapy and rituximab [Rituxan]-based treatment. If they do not achieve a CR—if they have a partial remission or stable disease—then those patients would be candidates for enrolling in this trial and [receive] rapcabtagene autoleucel as a next step. [Overall, we’re] trying to understand if we can deepen the responses in those patients with high-risk features in the frontline setting.

Disclosures: Dr Riedell reports receiving honoraria from Adaptive Biotechnologies; research funding from Tessa Therapeutics, Cargo Therapeutics, Calibr, CRISPR Therapeutics, Xencor, Fate Therapeutics, Cellectis, Kite/Gilead, Novartis, Genentech/Roche, Bristol-Myers Squibb; membership on the board of directors or advisory committees for Kite/Gilead, Novartis, Nektar Therapeutics, Abbvie, BeiGene, Bristol-Myers Squibb, Genmab, and Intellia Therapeutics; and serving as a consultant for Pharmacylics, Janssen, CVS Caremark, Nektar Therapeutics, Sana Biotechnology, Abbvie, Genentech/Roche, BeiGene, Bristol-Myers Squibb

Reference

Riedell PA, Kwon M, Flin IW, et al. Rapcabtagene autoleucel (YTB323) in patients (Pts) with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL): Phase II trial clinical update. Blood. 2024;144(suppl 1):67. doi:10.1182/blood-2024-204264