PHASE‐2 FIRST‐IN‐INDIA INDUSTRY STUDY OF VARNIMCABTAGENE AUTOLEUCEL (IMN‐003A) IN RELAPSED REFRACTORY B CELL MALIGNANCIES: IMAGINE STUDY B‐NHL SUBANALYSIS (2023)

Introduction: Varnimcabtagene autoleucel (IMN-003A) is an autologous CD19 directed CAR-T with 4-1BB co-stim domain and A3B1 binder, a non-FMC63 murine scFv, manufactured in India for phase 2 study in patients (pts) with relapsed / refractory (r/r) B cell malignancies (CTRI/2022/03/041162). Target dose (B-ALL: 1 × 106 CAR+ cells/kg; B-NHL: 5 × 106 CAR+ cells/kg) was infused as 3 fractions (10%, 30%, 60%) after Flu-Cy lymphodepletion. B-NHL subanalysis is presented here. Methods: Pts ≥ 18 yrs with r/r B-NHL, measurable disease, ≥1 prior regimen and ECOG 0-1 were eligible. IMN-003A persistence was evaluated by ddPCR. Manufacturing was in CliniMACS Prodigy. CAR-T % transduction and T cell subsets were analyzed by flow. Primary objectives were overall response rate (ORR: CR + PR; IWG criteria) at day +90, and occurrence of adverse events. Results: Of 23 pts in study, 11 pts with B-NHL (median 53 yrs, range 31–66) underwent apheresis with 100% manufacturing success (median time 15d; range 11–27). Two needed second apheresis. Mean % transduction was 28.27% (range 8.50–51.07) with median transgene copies / genome of 2.36 (range 0.76–4.16). Mean CD4/CD8 ratio was 0.31 (apheresis); 0.62 (final product FP); 2.05 (Day 0) and 0.23 (Day 90) with reversal post infusion. Mean proportion of naïve cells (CCR7+ RA+) was >35% in FP (Fig 1A). Median Product Doubling time was 1.03d (range 0.88–2.12) and Apheresis to Infusion time was 30d (range 21–95). Max IMN-003A expansion (Tmax) was at median 10d (range 7–21) with median Cmax 122,029 CAR copies / μg gDNA (range 24,624–284,498). IMN-003A persistence was 100% at D+28 and 40% at D+90 (range 28–NR) with concurrent B cell aplasia (Fig 1B) range 90–NR. CD4+ T cell count recovery (>200/μL) was seen at median of 24.5 days (range 7- 42) post infusion. Of 9 pts infused, 4 (44.4%) needed bridging therapy (patient characteristics in Figure 1D). Median follow-up was 99 days (range 58–226). Overall response rate (ORR) was 88.8% at D+28 and 71.4% at D+90. Median time to first response was 28 days. Median progression-free survival (PFS) and overall survival (OS) were not reached (Figure 1C). AESIs reported were CRS (Grade [G] 1 77.8%; G3+ 0%; overall 77.8%); ICANS (G1 0%; G3+ 0%; overall 0%); hypogammaglobulinemia (8/9, 5 recd IVIg) neutropenia (G3+ 100%); anemia (G3+ 55.6%); and thrombocytopenia (G3+ 22.2%). CRS median onset was D+3 and duration 3 days. No G3+ ICANS was reported. Tocilizumab usage was in 33.3% pts (majority for persistent G1 CRS). There was no treatment related mortality with one death due to disease progression. The research was funded by: Immuneel Therapeutics Private Limited Keywords: Aggressive B-cell non-Hodgkin lymphoma, Cellular therapies, Indolent non-Hodgkin lymphoma Conflicts of interests pertinent to the abstract S. Dhar Employment or leadership position: Immuneel Therapeutics Private Limited A. Kumar MG Employment or leadership position: Immuneel Therapeutics Private Limited J. Kumar Employment or leadership position: Immuneel Therapeutics Private Limited S. Yadav Employment or leadership position: Immuneel Therapeutics Private Limited P. Arasu Employment or leadership position: Immuneel Therapeutics Private Limited S. R. Elluru Employment or leadership position: Immuneel Therapeutics Private Limited M. M. Akheel Employment or leadership position: Immuneel Therapeutics Private Limited R. Nahar Employment or leadership position: Immuneel Therapeutics Private Limited A. Kamat Employment or leadership position: Immuneel Therapeutics Private Limited Stock ownership: Immuneel Therapeutics Private Limited