Evaluating Lyell’s CAR-T IMPT-314 in LBCL
Sarah Larson, MD, the medical director of the Immune Effector Cell Therapy Program at UCLA, discussed initial data from a phase 1/2 trial.
Sarah Larson, MD
Credit: UCLA
Lyell Immunopharma’s IMPT-314, a CD19/CD20 dual-targeted autologous chimeric antigen receptor T-cell (CAR-T) therapy, is currently being evaluated in a phase 1/2 clinical trial (NCT05826535) for the treatment of relapsed/refractory large B-cell lymphoma (LBCL). At the 66th American Society of Hematology (ASH) Annual Meeting and Exposition, held December 7-10, 2024, in San Diego, California, initial results from this trial were presented by Sarah Larson, MD, the medical director of the Immune Effector Cell Therapy Program in the Division of Hematology/Oncology at David Geffen School of Medicine at University of California, Los Angeles (UCLA).
Shortly after the conference, CGTLive® spoke with Larson to get an overview of the key results and future plans for the investigational product. Larson emphasized the favorable safety and efficacy findings seen so far, but noted that longer follow-up is needed.
CGTLive: Could you give some background about your presentation at ASH?
Sarah Larson, MD: IMPT-314 is a CD19/CD20-targeted "OR"-gate tandem CAR that is in naive memory T-cells. The reason for this design is to overcome 2 of the main mechanisms of resistance to CAR T-cells, the first one being antigen escape—that's why 2 antigens are targeted—and being placed in naive memory cells, which also improves persistence.
What were the key results that your presented?
The results of the first-in-human phase 1 trial of IMPT-314 was recently presented at the ASH meeting. The results are very favorable, with an overall response rate of 94% and a complete response rate of 71%. These very promising efficacy results were also accompanied by a very favorable toxicity profile. Only grade 1 and 2 cytokine release syndrome (CRS) were noted—there was no grade 3 CRS—and immune effector cell-associated neurotoxicity syndrome (ICANS) was predominantly grade 1/2, as well. The 3 patients that developed grade 3 ICANS resolved without any intervention above what's used in standard-of-care.
Were there any limitations in the study, or areas of interest that have been identified for more research?
I'm excited to see what the duration of response (DOR) and progression-free survival (PFS) are. The follow-up at this point is too short for that to have been presented. Both the DOR as well as PFS are not yet reached. I'll be excited to see that [because] the CD62L-selected cells we would expect to have better persistence, which we would hope then translates into a longer DOR and PFS.
Are there any future plans for this product that you can discuss, such as additional clinical trials?
I think in general, in the CAR T-cell space, moving it earlier and earlier into lines of therapy. Certainly, a product like this that has this kind of efficacy and favorable toxicity profile does make that possible to continue to move to earlier lines of therapy.
I think the only other notable part about this that's interesting is that this construct was initially developed at UCLA. Although I don't have the follow-up that's mature from the IMPT-314 study, the UCLA study has had a PFS of 50.1 months, with also a very favorable long-term toxicity profile. Again, that's part of what makes 314 so exciting because, again, we have the longer-term data from the UCLA trial.
Is there anything else you want to share?
For IMPT-314, the peak expansion was on Day 10, and the expansion was very favorable compared with other products at 94,000 copies per microgram of DNA. I think that also is very favorable that there were excellent kinetics of this product. Also the clinical trial is currently ongoing and enrolling diffuse LBCL patients in second-line and third-line plus.
This transcript has been edited for clarity.
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