C-CAR039 (also known as JNJ-90014496/prizlon-cel/prizloncabtagene autoleucel) which is a novel anti-CD20/CD19 bi-specific CAR T-Cell therapy is currently under investigation by Abelzeta (Previously Cellular Biomedicine) and Johnson & Johnson. During the EHA 2024 conference, updated results of C-CAR039 with additional patients and a longer follow-up of 30 months was presented. The C-CAR039 study is sponsored by Tianjin Medical University Cancer Institute and Hospital and the collaborator of the study is Cellular Biomedicine Group.

Between Nov 5, 2019, and Jan 11, 2022, 48 patients received C-CAR039 manufactured using the Miltenyi Biotec CliniMACS Prodigy System. Of the 48 patients, 44 patients had large B-cell lymphoma (LBCL) (Diffuse large B-cell lymphoma, n = 37; transformed Follicular Lymphoma, n=4; Primary Mediastinal Large B-cell lymphoma, n = 3), 3 patients had Follicular Lymphoma and 1 had Mantle Cell Lymphoma. The median age was 55 years (range, 25–71), and 11 (22.9%) patients were ≥ 65 years. 

As of September 25, 2023, Cytokine Release Syndrome (CRS) was present in 45 out of 48 individuals (93.8%), with just 1 (2.1%) having grade 3 symptoms. The median time to CRS onset was 3 days (range, 1–12), with a median duration of 5 days (range, 2–78). Three patients at the dose of 5.0 x106 CAR-T cells/kg had Immune effector cell-associated neurotoxicity syndrome (ICANS), of which 2 were grade 1 and 1 was grade 2. The median time to onset of ICANS was 6 days (range, 5–29), with a median duration of 12 days (range, 3–53). All CRS and ICANS were resolved. Grade 3 or higher cytopenias not resolved by Day 30 following C-CAR039 infusion included neutropenia (54.2%), anemia (20.8%) and thrombocytopenia (20.8%). Grade 3 or higher infections were observed in 12 (25.0%) patients. The second primary malignancy after C-CAR039 infusion was observed in 3 patients and none were related to C-CAR039. Fifteen deaths occurred, where 11 were due to disease progression, 2 were due to Adverse Events (AEs) of acute myeloid leukemia (AML), and 1 was due to an unknown cause.

Of the 48 patients, 47 were evaluable for efficacy (1 patient had no measurable disease at baseline). The overall response rate (ORR) and complete response (CR) rates were 91.5% and 85.1%, respectively. The median time to the first response and CR were 1.0 and 1.2 months, respectively. The 43 LBCL patients displayed 86.0% CR and 90.7% ORR, respectively. Median Overall survival (OS), progression-free survival (PFS), and median duration of response (DOR) were all not reached. At 24 months, the Kaplan-Meier (KM) estimation of the PFS and OS rates for all patients were 62.6% and 76.5%, respectively. 

The pharmacokinetic profile showed that C-CAR039 has a robust expansion and long-term persistence, with median Tmax and Tlast of 11.5 days and 216 days, respectively.

KOL insights

“The administration of CAR T-cell therapy in the outpatient setting was deemed feasible and safe in patients with relapsed/refractory non-Hodgkin lymphoma (NHL), according to findings from an exploratory analysis of real-world outpatient effectiveness shared during the 2024 EHA Congress” – MD, United States

Conclusion 

In patients with R/R B-NHL, anti-CD19 CAR T cell therapies have been shown to be successful. Data suggests that about 20% of LBCL patients and 10% of indolent patients are non-responders, and responders may relapse due to the development of CD19-negative tumor clones. The theory underlying this treatment is that CAR-T cells that target two different antigens may reduce the likelihood of recurrence by preventing antigen escape. In Phase I studies, patients with R/R NHL in China showed promising overall and complete response rates to these experimental CD20-directed autologous CAR-Ts. Most study participants had diffuse large B-cell lymphoma, which is the most common type of aggressive lymphoma and accounts for about one-third of B-cell lymphomas worldwide. 

Data from the study showed that C-CAR039 is a novel bispecific CAR-T targeting CD19 and CD20 B-Cell antigens. These encouraging data suggest that C-CAR039 is a promising dual-targeting CAR-T therapy for patients with B-NHL. It is worth highlighting that a registration study is ongoing at R2PD in Chinese patients with R/R LBCL (NCT05800977). 

Johnson & Johnson Innovative Medicine is going to conduct further studies on C-CAR039 in a global patient population (apart from Greater China). To research, manufacture, and commercialize next-generation CAR T-cell therapies for the treatment of B-cell malignancies, Johnson & Johnson Innovative Medicine and Cellular Biomedicine Group (now AbelZeta) signed a worldwide collaboration and licensing agreement in May 2023. Thanks to this partnership, Johnson Innovative Medicine was able to gain rights to C-CAR039, a bi-specific CAR-T that targets both CD19 and CD20, and C-CAR066 (also known as JNJ-90009530), a CAR-T that targets CD20. In an additional poster abstract (#P1452), the business provided the two-year follow-up data of C-CAR066.

C-CAR066 also demonstrated a manageable safety profile and a deep and durable response in patients with R/R LBCL who had failed from a prior CD19 CAR-T therapy. An open-label study (NCT05784441) in relapsed or refractory B-cell NHL  is ongoing.