Varnimcabtagene Autoleucel (IMN-003A): Differences in T Cell Subset Phenotype in B-ALL and B-NHL Cohorts Did Not Influence Efficacy Outcomes in the Phase-2 Study (IMAGINE)

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.6881-6881
• Main Authors: Bhat, Sunil, Damodar, Sharat, Thirumalairaj, Raja, Malhotra, Pankaj, Pulikkottil, Alex Jose, Kumar, Jeetendra, Soares, Melina, Dhar, Sudeshna, Shetty, Sandeepa, T.I., Mani Bharathi, Jakka, Gopinadh, Joseph, Anne Roshan, Kumar MG, Arun, Arasu, Pallavi, Elluru, Sri Ramulu, Akheel, Mohammed Manzoor, Chenji, Giridhar K, Gandikota, Lakshmikanth, Nahar, Rahul, Kamat, Anil
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-184521

Background: Varnimcabtagene autoleucel (IMN-003A) is an autologous CD19 directed CAR-T cell product with a 4-1BB co-stimulatory domain and a non-FMC63 murine single chain variable fragment (A3B1 binder), manufactured in India, tested in the IMAGINE study (CTRI/2022/03/041162), a phase-2 clinical trial for patients (pts) with relapsed and/or refractory B cell malignancies. A fractionated infusion of 1 x 10 6 CAR+ cells (IMN-003A)/kg for B-ALL cohort and 5 x 10 6 CAR+ cells (IMN-003A)/kg for B-NHL cohort was administered over 3 days (10%, 30%, 60%). Phenotypic data comparing the apheresis (AP) and final product (FP) from B-ALL and B-NHL cohorts, related manufacturing and clinical response observations are discussed in this abstract. Methods: IMN-003A was manufactured using the Miltenyi CliniMACS Prodigy®, a cGMP compliant closed system. The apheresis and final infusion product (FP) were analysed for percent CAR transduction and T cell subsets by flow cytometry. CAR copies in the final product were determined by ddPCR. Cell counts measured using automated Vi-cell counter were used to calculate fold expansion. Results: Apheresis PBMC from 25 patients in the IMAGINE study were selected for T-cells, transduced & expanded to achieve the FP, which was infused in 24 patients (1 patient withdrawn). Three patients needed a second apheresis and re-manufacturing to achieve the target dose. The FP comprised primarily of CD3+ T cells (median 99.38%, range 96.3 - 99.92%) with mean of 38.18% CAR+ T cells for B-ALL cohort (range: 20.28 - 58.35%) and significantly lower 27.53% CAR+ T-cells for B-NHL cohort (range: 8.5 - 51.07%, p=0.02). The vector copy number (VCN) however did not differ between the two cohorts (mean of 2.66 and 2.37 copies for B-ALL and B-NHL cohorts respectively; p=0.4). The fold expansion at Day 6 of manufacturing was also significantly lower for B-NHL cohort (6.93) compared to the B-ALL cohort (10.33, p=0.02). Consistent with the relatively more challenging manufacturing for the B-NHL cohort with 5 times higher target dose, it was observed that the mean proportion of naïve T-cells (CCR7 + CD45RA +) was lower in both AP (B-NHL 9.71%, B-ALL 27.24%, p