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2104 Primary Analysis of Varnimcabtagene Autoleucel (IMN-003A) in Phase 2 Study (IMAGINE), a First-in-India Industry CD19-Directed CAR-T Cell Therapy for Patients with Relapsed Refractory B Cell Malignancies

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster I
Hematology Disease Topics & Pathways:
Research, clinical trials, Lymphoid Leukemias, ALL, Biological therapies, Lymphomas, non-Hodgkin lymphoma, Clinical Research, B Cell lymphoma, Chimeric Antigen Receptor (CAR)-T Cell Therapies, Diseases, indolent lymphoma, aggressive lymphoma, Therapies, Lymphoid Malignancies, Minimal Residual Disease
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Sharat Damodar, MBBS, MD, DM1*, Sunil Bhat, MD1*, Raja Thirumalairaj, MD DM2*, Pankaj Malhotra, MD3, Akshatha Nayak, MD1*, Pooja Mallya, MD1*, Ravi Joshi, MD1*, Revathy Raj, MD2*, Rameez Ahamed, MD2*, Charanpreet Singh, MD, MBBS, DM3*, Deepak MB, MD1*, Sudarshan Chougule, MD1*, Lakshman Vaidhyanathan, MD2*, Man Updesh Singh Sachdeva, MD3*, Karthik GA, MD1*, Sunil HV, MD1*, Jayaraj Govindaraj, MD2*, Shelley Simon, MD2*, Rajender Kumar Basher, MD3*, Sudeshna Dhar4*, Arun Kumar MG4*, Pallavi Arasu4*, Sri Ramulu Elluru4*, Mohammed Manzoor Akheel, MPH MBA4* and Anil Kamat, MD FRCP FRCPath MBA4

1Mazumdar Shaw Medical Centre, Narayana Health City, Bengaluru, India
2Apollo Speciality Hospital, Chennai, India
3Postgraduate Institute of Medical Education and Research, Chandigarh, India
4Immuneel Therapeutics Private Limited, Bengaluru, India

Background: Varnimcabtagene autoleucel (IMN-003A) is an autologous second-generation CAR-T cell product with a 4-1BB co-stimulatory domain and a non-FMC63 based murine single chain variable fragment targeting CD19 (A3B1 binder), manufactured in India. Preclinical and Phase 1 study was conducted at HCB / IDIBAPS Spain. Here, we present the primary analysis of IMAGINE, a Phase 2, multicenter, single-arm study of var-cel for patients in India with relapsed/refractory B cell malignancies (RR BCM) (CTRI/2022/03/041162).

Methods: Patients (pts) aged 3 to 45 years (B-ALL) and ≥ 18 years (B-NHL) with RR BCM were eligible if they had measurable disease, as assessed by lymphoid blasts (B-ALL) or metabolic tumour bulk (B-NHL), received ≥1 prior regimen, refractory to the last line of treatment with good performance status (ECOG 0 to 1). Bridging therapy was allowed after apheresis. Cyclophosphamide (300 mg/m2) and fludarabine (30 mg/m2) on days -5 to -3 were used as preparative lymphodepletion regimen. The target dose was 1x106/kg CAR+ cells (B-ALL) and 5x106/kg CAR+ cells (B-NHL) (overall range 0.1x106 to 5x106) and was administered in a fractionated manner (10%/30%/60%) over 3 days with at least 24h between infusions. Primary objectives were overall response rate (ORR: CR + CRi in B-ALL and CR + PR in B-NHL) at day +90 after first infusion, and safety. Response was assessed as per NCCN (B-ALL) and IWG (B-NHL) criteria; bone marrow minimal residual disease (MRD) for B-ALL was analyzed by flow cytometry at 10-4 sensitivity and PET-CT for B-NHL. Adverse events (AEs) were graded using CTCAE v5.0. CRS and ICANS were graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) criteria.

Results: At data cut-off, of 25 pts enrolled (median age 31 yrs, range 3 - 66) with RR BCM [n=13 B-ALL, median blasts 0.34% (range 0.01 - 27.2); n=12 B-NHL, median TMTV 67.9 ml (range 27.1 - 1177), median SPD 3846 mm2 (range 1001 to 35849], 24 pts received var-cel (1 withdrawal) with majority of infusions on Days 0, +3, +7 and 12 pts (50%) needed bridging therapy. Median CAR-T cell manufacturing time was 14 days (range 10 - 27) with 100% manufacturing success.

Median follow-up after IMN-003A administration was 205 days (range 12 – 434). Overall response rate (ORR) was 91.7% (22/24) at D+28 (B-ALL 91.7%, MRD neg 83.3% (n=10/12); B-NHL 91.7%, CR 66.7%) and 80.9% (17/21) at D+90 [B-ALL 80%, MRD neg 80% (n=8/10); B-NHL 81.8% (9/11), CR 63.6%]. One B-NHL pt in PR at D+28 achieved CR at D+90. Three pts relapsed by D+90. Of MRD evaluable pts, response was 100% at day+28 (n=11/11) and 88.9% at D+90 (n=8/9). Median time to first response was 28 days.

Median progression free survival (PFS, range 12-NR), duration of response (DOR, range 0-NR) and overall survival (OS) were not reached (range 12-NR).

AESIs reported were CRS (Grade [G] 1 62.5%; G3+ 4.2%; overall 66.7%); ICANS (G1 4.2%; G3+ 0%; overall 4.2%); neutropenia (G3+ 91.7%; overall 100%); anemia (G3+ 29.2%; overall 95.8%); and thrombocytopenia (G3+ 20.8%; overall 91.7%). CRS median onset was D+5 and duration 3 days. No G3+ ICANS was reported. Tocilizumab, steroids and anakinra usage was in 37.5% (n=9/24, majority for persistent G1 CRS), 8.3% and 4.2% respectively. Treatment related mortality was 4.2% (n=1/24); 3 pts died of disease progression.

IMN-003A cells demonstrated peak expansion on D+10 (range 7 – 28 days). 79.2% at D+28 and 29.2% at D+90 had measurable CAR+ T cells in peripheral blood; median D+28 (range D+10 - NR). Updated results will be presented in the meeting.

Conclusions: Varnimcabtagene autoleucel (IMN-003A), a First-In-India Industry CD19-directed CAR-T Cell Therapy for RR BCM, has demonstrated manageable safety profile and durable efficacy outcomes with deep responses including absence of severe neurotoxicity. This offers a significant benefit over standard treatment options for patients with RR BCM.

Disclosures: Dhar: Immuneel Therapeutics Private Limited: Current Employment. Kumar MG: Immuneel Therapeutics Private Limited: Current Employment. Arasu: Immuneel Therapeutics Private Limited: Current Employment. Elluru: Immuneel Therapeutics Private Limited: Current Employment. Akheel: Immuneel Therapeutics Private Limited: Current Employment. Kamat: Immuneel Therapeutics Private Limited: Consultancy.

*signifies non-member of ASH