Nirav N. Shah, MD, associate professor at the Medical College of Wisconsin in Milwaukee, discussed the evaluation of LV20.19 CAR in MCL, as well as key efficacy and safety data on the therapy to date.
A version of this interview originally appeared on our sister site, OncLive®.
At the 2023 Transplantation and Cellular Therapy Meetings, follow-up data from the phase 2 cohort of a single-center, prospective, phase 1/2 study (NCT04186520) evaluating the safety and efficacy of LV20.19 CAR in adult patients with B-cell malignancies who progressed on prior therapies were presented. Ultimately, the data showed that those receiving LV20.19 CAR experienced an overall response rate (ORR) of 100% at day 28 (n = 14).1
Similarly, complete (CR) and partial response (PR) rates were 71% and 29%, respectively. At 90 days, the ORR was unchanged, and the CR rate increased to 92% (n = 11). The median overall survival (OS) and progression-free survival (PFS) were not reached after 22 months of follow-up, nor were any no instances of grade 3/4 cytokine release syndrome (CRS) observed. The rate of grade 3/4 immune effector cell–associated neurotoxicity syndrome (ICANS) was 14%.1
LV20.19 CAR is a lentiviral bispecific CAR T-cell therapy targeting both CD19 and CD20 B-cell antigens, being assessed for mantle cell lymphoma (MCL) treatment. Thus far, improved responses and favorable toxicity profiles have been observed, suggesting this as a possibly method maximize patient benefit with CAR T-cell therapy, according to Nirav N. Shah, MD, who presented the data at Tandem 2023.
Previously, the safety, efficacy, and optimal dose of LV20.19 CAR was evaluated in a prior phase 1 dose-escalation and -expansion study (NCT03019055) in patients with relapsed/refractory B-cell non-Hodgkin lymphoma or chronic lymphocytic leukemia. The trial established the target dose of LV20.19 CAR at 2.5 × 106 cells/kg and showed that the on-site manufacturing and infusion of LV20.19 CAR was safe, effective, and tolerable.2
Shah, who is an associate professor at the Medical College of Wisconsin in Milwaukee, spoke with OncLive, a sister publication of CGTLive, about the choice to evaluate LV20.19 CAR in MCL, key efficacy and safety data from the follow-up study of this agent, and ongoing efforts to potentially expand its use across other B-cell malignancies.
Nirav N. Shah, MD: This is a follow-up study [using] a construct we had initially worked on called zamtocabtagene autoleucel, [or] LV20.19 [CAR]. It’s a dual-targeted CAR T-cell [therapy]. We had previously completed and published a phase 1 [trial, showing] an exciting overall response rate [with this agent], and identifying the safe dose level [in refractory B-cell malignancies]. We developed a follow-up study to better understand this CAR T-cell product.
This single-center study specifically looked at patients with MCL [and was designed] as a pilot clinical trial. We chose MCL [because] it is a unique non-Hodgkin lymphoma which [has] known high levels of CD20 expression. [In] a disease with high levels of CD20, drugs like rituximab [Rituxan] have been shown to [elicit] survival benefit by targeting CD20. We thought that this CAR T-cell construct would be optimally primed [for MCL] because it targets [both] CD19, which we know is effective in MCL based on prior CAR T-cell approvals, and CD20.
This was a phase 1/2 study [with] a 14-patient, single-stage, design. We based our calculations on the 3-month CR rate in the pivotal [PCYC-1104 trial (NCT01236391)] of ibrutinib [Imbruvica; Pharmacyclics/Janssen Biotech] for relapsed/refractory MCL and targeted a 50% 3-month CR rate. We were going to call this a positive study if we had 6 or more patients who achieved a CR by day 90. We have now achieved that end point.
The ORR at day 28 was 100%, and the majority of those [responses] were CRs. [Specifically], 71% of [responses] were CRs, and 29% were PRs. At day 90, the ORR was still 100%. Some patients converted from a PR to a CR, so the CR rate was 92%. In the phase 2 cohort, we now have 8 patients with a CR at day 90. We do consider this to be a positive clinical trial. We [also] have reasonable follow-up on these patients. [At] a median follow-up of 22 months, there’s been 1 relapse [among] 14 patients.
Overall, the safety profile was in-line with other histologies that we have treated with this product. CRS did occur in 93% of patients. Only 21% of patients had neurotoxicity. Two patients had grade 3/4 ICANS and 1 patient had grade 1/2 ICANS. No patients required intensive care unit–level care in the first 28 days.
We did have 1 nonrelapse mortality. [This] was a high-risk patient who had relapsed [after] prior allogeneic transplant for MCL and then got CAR T-cell therapy. He passed away from gram-negative sepsis at day [46, which was] outside of the dose-limiting toxicity period. Beyond that, [the regimen] was well tolerated, and all [other] patients remain alive.
We’re really excited by these outcomes. The safety profile and efficacy profile of this CAR T-cell product are favorable compared [with] what’s currently available. We launched a phase 2 trial in diffuse large B-cell lymphoma, and I’m working with our partners to codevelop a similar multicenter trial with the CD20/CD19 CAR T-cell product in MCL. That trial is under development now, [and aims] to see if we can [confirm] these single-center results in a multicenter setting.
[Although LV20.19 CAR] has different names depending on whether it’s a single-center or industry-sponsored study, we’re fundamentally talking about the same construct. It’s exciting that we’re showing feasibility, efficacy, and safety [with this construct] in different patient populations and in different clinical trials.
Some exciting data [were presented] in the late-breaking abstract session. There’s data coming out about CD22 CAR T cells being given as a second[-line therapy] for patients who have relapsed after CD19-based [therapy]. That’s an area of unmet need, and the data look exciting. The transplant meeting [also showed] exciting data on stem cell and allogeneic stem cell transplant. I [enjoy] gathering live, getting to collaborate with colleagues, and seeing all the cutting-edge data.
Transcript edited for clarity.
Disclosures: Shah disclosed advisory roles with Legend, Epizyme, TG Therapeutics, Kite Pharma, Novartis, LOXO-Lilly Oncology, Janssen, BMS-Juno, Seagen; researcher roles with Miltenyi Biotec and LOXO-Lilly Oncology; consultant roles with Miltenyi Biotec, Lilly Oncology, and Incyte; and a member/founder role with Tundra Therapeutics.