rapcabtagene autoleucel (YTB323) / Novartis - LARVOL DELTA

Phase 2 Study Evaluating Rapcabtagene Autoleucel in Participants With Severe Active GPA or MPA (clinicaltrials.gov) - P2 | N=126 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • ANCA Vasculitis • Rare Diseases • Vasculitis

An Open-label, Study to Assess Safety, Efficacy and Cellular Kinetics of YTB323 in Severe, Refractory Systemic Lupus Erythematosus (clinicaltrials.gov) - P1/2 | N=21 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

Clinical, Cellular Kinetics, Pharmacodynamics and Biomarker Data Up to 12 Months After YTB323 (Rapcabtagene Autoleucel), a Rapidly Manufactured CD19 CAR-T Therapy, From an Open-Label, Phase 1/2 Study in Severe Refractory SLE (EULAR 2025) - No abstract available

Biomarker • Clinical • IO biomarker • P1/2 data • PK/PD data • Inflammatory Arthritis

Phase 2 Study Evaluating Rapcabtagene Autoleucel in Participants With Severe Active GPA or MPA (clinicaltrials.gov) - P2 | N=126 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P2 trial • ANCA Vasculitis • Rare Diseases • Vasculitis

Next-generation CAR-T treatment begins domestic clinical trials…Beyond cancer to immune diseases? [Google translation] (Health Korea News) - "The Ministry of Food and Drug Safety approved the 2b phase clinical trial plan (IND) for 'YTB323' on the 14th. The trial is to compare the efficacy and safety of 'YTB323' with standard therapy in patients with systemic lupus erythematosus (SLE) accompanied by active and refractory lupus nephritis (LN)....Therefore, the approval date for 'YTB323' is expected to be around 2029, about four years from now, and its introduction in Korea is expected to be even later, after 2030."

Korea approval • Launch non-US • New P2b trial • Lupus Nephritis • Systemic Lupus Erythematosus

RAPCABTAGENE AUTOLEUCEL (YTB323) IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL): UPDATED RESULTS FROM A PHASE II CLINICAL TRIAL (EHA-EBMT-CART 2025) - No abstract available

Clinical • P2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Open-label, Multi-center, Phase I/II Study to Assess Safety, Disease Progression and Cellular Kinetics Following YTB323 Administration in Participants With Non-active Progressive Multiple Sclerosis (PMS) (clinicaltrials.gov) - P1/2 | N=28 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Multiple Sclerosis

Rapcabtagene autoleucel: Regulatory submission for SLE/lupus nephritis in 2028 or later (Novartis) - Q4 & FY2024 Results: Regulatory submissions for myositis, systemic scleroderma and high risk large B-cell lymphoma in 2028 or later

Filing • Diffuse Large B Cell Lymphoma • Immunology • Lupus Nephritis • Myositis • Oncology • Scleroderma • Systemic Lupus Erythematosus

Study to Assess Safety, Efficacy, and Cellular Kinetics of YTB323 in Generalized Myasthenia Gravis (clinicaltrials.gov) - P1/2 | N=15 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Myasthenia Gravis

MODULE 5: Chimeric Antigen Receptor (CAR) T-Cell Therapy and Other Novel Strategies for CLL (ASH 2024) - "This program is supported by educational grants from AstraZeneca Pharmaceuticals LP, BeiGene Ltd and Eli Lilly.Biological rationale for the investigation of CD19- directed CAR T-cell therapy for CLL Published efficacy and safety findings with lisocabtagene maraleucel (liso-cel) for R/R CLL from the Phase I/II TRANSCEND CLL 004 trial FDA approval of liso-cel for CLL previously treated with a BTK inhibitor and a Bcl-2 inhibitor; current clinical role and optimal patient selection Early findings with other CAR T-cell-based approaches (eg, liso-cel in combination with ibrutinib, brexucabtagene autoleucel, rapcabtagene autoleucel) for heavily pretreated CLL Antitumor activity observed with bispecific antibody therapy (eg, epcoritamab, NVG-111, LAVA-051) for CLL, including in patients with Richter's transformation Other promising agents and strategies under investigation for CLL"

Chronic Lymphocytic Leukemia • Oncology • Richter's Syndrome

Real-World Outcomes of Patients with High-Grade B-Cell Lymphoma with MYC and BCL2 rearrangements Treated in the Contemporary Era (ASH 2024) - "Front-line induction therapy included R-CHOP (n=29), DA-R-EPOCH (n=29), R-CODOX-M/IVAC (n=4), Pola-R-CHP + glofitamab (n=2), R-ICE (n=2), R-HyperCVAD/MA (n=1), obinutuzumab (G)-CHOP (n=1), R-CHOP + glofitamab (n=1), R-CHOP + tafasitamab (n=1), R-CHOP + lenalidomide (n=1), DA-G-EPOCH (n=1), and R-ESHAC (n=1), as well as palliative regimens including R-mini-CHOP (n=2), PEP-C (n=1), and rituximab + prednisolone (n=1)...Nineteen patients received CAR-T therapy (8 at first relapse, 11 at subsequent relapse), including axicabtagene ciloleucel (n=10), tisagenlecleucel (n=5), rapcabtagene autoleucel (n=2), and CTX110 (n=2); the 4-year PFS and OS rates from date of CAR-T infusion were 62% and 55%, respectively. Conclusions : Our series indicates that intensification of front-line induction in patients with HGBL-MYC/BCL2-R maximizes first response and PFS, and incorporation of CNS prophylaxis into initial therapy minimizes risk of CNS relapse and improves OS. CAR-T represents a..."

Clinical • Real-world • Real-world evidence • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • MYC

An Open-label Study to Assess the Safety, Efficacy, and Cellular Kinetics of YTB323 in Relapsing Multiple Sclerosis (clinicaltrials.gov) - P1/2 | N=28 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • CNS Disorders • Multiple Sclerosis

Rapcabtagene Autoleucel (YTB323) in Patients (Pts) with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (R/R DLBCL): Phase II Trial Clinical Update (ASH 2024) - P1/2 | "28 pts (44%) received lower-dose lymphodepletion (LD) (fludarabine/cyclophosphamide [flu/cy] 25/250 mg/m2 for 3 d), median FU 32.8 mo, and 33 pts (52%) received higher-dose LD (flu/cy 30/500 mg/m2 for 3 d), median FU 5.4 mo. 2 pts (3%) received bendamustine (90 mg/m2) LD...Conclusions : At the 12.5x106 CAR+ cell dose, rapcabtagene autoleucel showed promising efficacy and a favorable safety profile. Although pt numbers were limited, risk-benefit analysis supports use of the lower-dose LD regimen before infusion; continued assessment of long-term efficacy and safety outcomes is needed."

Clinical • P2 data • Anemia • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Thrombocytopenia • BCL2 • BCL6 • MYC

Preliminary results from a phase 1/2 study evaluating the safety, cell kinetics and efficacy of rapcabtagene autoleucel (YTB323) a CAR-T targeting CD19 in patients with severe refractory systemic lupus erythematosus (srSLE) [Google translation] (Rev Rhum Ed Fr) - P1/2 | N=24 | NCT05798117 | Sponsor: Novartis Pharmaceuticals | "Between April 2023 and March 2024, 11 patients with srSLE received treatment with YTB323. We report preliminary safety, efficacy, and biomarker data for these 11 patients (data cutoff: March 2024). As expected, transient cytopenia, including grade 3 or 4, was observed in all 11 patients, including anemia ( n=6 ; grade 2 [ n=2] or 3 [ n=4]) and neutropenia ( n=8, grade 3 [ n=2] or 4 [ n=6]). Hypogammaglobulinemia, not requiring treatment with intravenous immunoglobulins, occurred in 6 patients. Cytokine release syndrome (CRS) was observed in 6 patients (grade 1 [ n=3] or 2 [ n=3]) with resolution under tocilizumab. Immune cell-associated neurotoxicity syndrome (ICANS), manifesting as transient ataxia, was reported in 1 patient (grade 2). Grade 2 infectious complications included pneumonia ( n=1) and a urinary tract infection ( n=1)."

P1/2 data • Systemic Lupus Erythematosus

Phase 2 Study of Rapcabtagene Autoleucel in Myositis (clinicaltrials.gov) - P2 | N=123 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Immunology • Myositis

Rapcabtagene Autoleucel Shows Promise for DLBCL in Updated Phase 2 Data (CGTLive) - P1/2 | N=225 | NCT03960840 | Sponsor: Novartis Pharmaceuticals | "The CD19-directed CAR T-cell therapy rapcabtagene autoleucel (YTB323) showed high rates of complete remission (CR) and a favorable safety profile for patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to updated findings from a phase 2 study (NCT03960840) presented at the 2024 ASH Annual Meeting...Across 60 patients with DLBCL who received rapcabtagene autoleucel at a dose of 12.5 x 10⁶ CAR+ cells at least 25 days before data cutoff, the overall response rate (ORR) was 88.3% (95% CI, 77.4%-95.2%). The CR rate was 65% (95% CI, 51.6%-76.9%). Responses were durable, with 53.9% of patients continuing to respond at 12 months. Of those with a best response of CR, the 12-month duration of response rate was 69.1%. Some patients were able to achieve a CR from their bridging therapy. When these patients were excluded (n = 4), the CR rate with rapcabtagene autoleucel was 62.5%."

P2 data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Phase 2 Study Evaluating Rapcabtagene Autoleucel in Participants With Diffuse Cutaneous Systemic Sclerosis (clinicaltrials.gov) - P2 | N=86 | Recruiting | Sponsor: Novartis Pharmaceuticals

New P2 trial • Immunology • Scleroderma • Systemic Sclerosis

Study to Assess Safety, Efficacy, and Cellular Kinetics of YTB323 in Generalized Myasthenia Gravis (clinicaltrials.gov) - P1/2 | N=15 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P1/2 trial • CNS Disorders • Myasthenia Gravis

Novartis highlights new 96-week results from Phase III Scemblix ASC4FIRST trial at ASH and late-breaking analysis from Phase III Kisqali NATALEE trial at SABCS (GlobeNewswire) - "Novartis will present data from more than 65 abstracts, including investigator-initiated trials at the 66th American Society of Hematology (ASH) Annual Meeting & Exposition and the 2024 San Antonio Breast Cancer Symposium (SABCS)....Longer-term 96-week results from Scemblix ASC4FIRST Phase III study in first-line Ph+ CML-CP to be presented following recent FDA approval based on 48-week data. Late-breaking Kisqali 4-year analysis on distant disease-free survival in key subgroups with HR+/HER2- early breast cancer from Phase III NATALEE trial also to be presented."

Clinical data • Late-breaking abstract • P3 data • Diffuse Large B Cell Lymphoma • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Myelofibrosis

Phase 2 Study of Rapcabtagene Autoleucel in Myositis (clinicaltrials.gov) - P2 | N=123 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P2 trial • Immunology • Myositis

Rapcabtagene: Regulatory submission for high risk large B-cell lymphoma in 2027 or later (Novartis) - Q3 2024 Results

Filing • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Oncology

Open-label, Multi-center, Phase I/II Study to Assess Safety, Disease Progression and Cellular Kinetics Following YTB323 Administration in Participants With Non-active Progressive Multiple Sclerosis (PMS) (clinicaltrials.gov) - P1/2 | N=28 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P1/2 trial • CNS Disorders • Multiple Sclerosis

CYTB323A12101: Phase I/II Study of Rapcabtagene Autoleucel in CLL, 3L+ DLBCL, r/r ALL and 1L HR LBCL (clinicaltrials.gov) - P1/2 | N=225 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jun 2027 ➔ May 2028

Trial completion date • Acute Lymphocytic Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Small Lymphocytic Lymphoma • BCL2 • BCL6

An Open-label Study to Assess the Safety, Efficacy, and Cellular Kinetics of YTB323 in Relapsing Multiple Sclerosis (clinicaltrials.gov) - P1/2 | N=28 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P1/2 trial • CNS Disorders • Multiple Sclerosis

A Study of Rapcabtagene Autoleucel in Systemic Lupus Erythematosus (SLE) Patients With Active, Refractory Lupus Nephritis (LN) (clinicaltrials.gov) - P2 | N=144 | Recruiting | Sponsor: Novartis Pharmaceuticals

New P2 trial • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus