huCART19-IL18 / University of Pennsylvania - LARVOL DELTA

Enhanced CAR T-Cell Therapy for Lymphoma after Previous Failure. (PubMed, N Engl J Med) - P1 | "In this small study, huCART19-IL18 had a safety profile consistent with other CAR T-cell treatments and showed promising efficacy at low cell doses in patients with lymphoma after the failure of previous anti-CD19 CAR T-cell therapy. (ClinicalTrials.gov number, NCT04684563.)."

Journal • Hematological Malignancies • Lymphoma • Oncology • IL18

IL18-armored CAR T cells in relapsed/refractory B cell acute lymphoblastic leukemia (ASH 2025) - P1 | "NEJM 2025), and here we share our initial experiencetreating patients with R/R B cell acute lymphoblastic leukemia (ALL).MethodsIn a single center, first in human clinical trial utilizing huCART19-IL18 (NCT04684563), adult patients withR/R CD19+ ALL were eligible, including those with CNS disease and those with relapses after priorCART19, blinatumomab, and allogeneic transplant (alloHCT)...Subjects then receivedlymphodepleting (LD) fludarabine and cyclophosphamide followed by huCART19-IL18 infusion.ResultsAs of Aug...Subjects had a median of 5 (3-11) priorlines of therapy including alloHCT in 4 patients, blinatumomab in 4 (3 as salvage for post-alloHCT relapse),and brexucabtagene autoleucel in 2...Three patients received tocilizumab for CRS, and 1 received corticosteroids andanakinra for ICANS...All treated patients withadequate follow-up achieved early MRD-negative CR (including in the CNS), and there have been norelapses or deaths with a median follow-up of 15.1..."

CAR T-Cell Therapy • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • CNS Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • IL18

Safety and efficacy of armored huCART19-IL18 in patients with relapsed/refractory lymphomas that progressed after anti-CD19 CAR T cells. (ASCO 2024) - P1 | "Treatment with huCART19-IL18 has an acceptable safety profile and produced durable remissions in heavily pre-treated pts with R/R NHL despite prior CAR T-cell therapy. The subtype of the preceding CAR product may influence the expansion and effectiveness of huCART19-IL18."

CAR T-Cell Therapy • Clinical • Diffuse Large B Cell Lymphoma • Fatigue • Hematological Malignancies • Hypotension • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • IL18

IL18-Armored CAR T-Cell Therapy Produces Deep and Sustained Responses for Heavily Pretreated B-Cell Acute Lymphoblastic Leukemia (HMP Global) - "At 3 months post-infusion, ORR 100% with CR 80%; all MRD-evaluable patients achieved MRD-negative CR, and a CNS-only case achieved complete CNS remission. With median follow-up 19.6 months, no relapses or deaths were observed; some patients demonstrated long-term CAR persistence in blood/CSF, and successful retreatment-maintained remission."

P1 data • B Acute Lymphoblastic Leukemia • B Cell Non-Hodgkin Lymphoma • Chronic Lymphocytic Leukemia

huCART19-IL18-eDHFR Cells in Relapsed/Refractory Follicular Lymphoma (clinicaltrials.gov) - P1 | N=6 | Not yet recruiting | Sponsor: University of Pennsylvania

New P1 trial • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • CD19

IL18-armored CAR T cells in patients with CLL/SLL and Richter's transformation after prior BTK inhibitor and venetoclax failure (ASH 2025) - "Background : The rate of complete remission (CR) in the pivotal trial that led to FDA approval oflisocabtagene maraleucel (liso-cel) for chronic lymphocytic leukemia/small lymphocytic lymphoma(CLL/SLL) was only 18% in patients (pts) after BTK inhibitor (BTKi) and venetoclax (ven) failure (Siddiqi etal, Lancet 2023)...Theproduct is administered as a single intravenous infusion 2 to 5 days after lymphodepleting (LD)chemotherapy with bendamustine (90 mg/m2) x 2 days...Two pts received bridging therapy(obinutuzumab in 1, radiation in 1); an additional 3 were on a novel agent that started prior apheresisand continued until LD chemo (BTKi in 2, ven in 1)...The median CRS duration was 6 days (range 2-10), and tocilizumab was used in 5 (71%) cases... In the CLL/SLL and RT cohort, huCART19-IL18 produced durable remissions in heavily pre-treated pts after prior failure of a BTKi and ven. Following DL de-escalation, the treatment had amanageable toxicity profile. Our data supports..."

CAR T-Cell Therapy • Clinical • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Richter's Syndrome • Small Lymphocytic Lymphoma • IL18 • TP53

UPCC15420: huCART19-IL18 in CD19+ Cancers (clinicaltrials.gov) - P1 | N=72 | Active, not recruiting | Sponsor: University of Pennsylvania | Recruiting ➔ Active, not recruiting

Enrollment closed • Acute Lymphocytic Leukemia • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Chronic Myeloid Leukemia • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ALK • BCL2 • BCL6 • CD19

Evaluation of huCART19-IL18 Manufactured Using Synecta™ CDNP Technology to Improve CAR‑T Yield and Consistency in Cohort D of an Ongoing Phase I Study (NCT04684563) (SITC 2025) - P1 | "Cohort D is currently open and actively recruiting. No clinical data from this cohort have been reported to date.Trial Registration NCT04684563"

IO biomarker • P1 data • Chronic Lymphocytic Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • IL18

Next-generation "armored" CAR T cell therapy shows promising results in lymphoma patients (News-Medical) - P1 | N=72 | NCT04684563 | "The new therapy diminished cancer in 81 percent of patients and resulted in complete remission in 52 percent, with some of the earliest patients treated experiencing durable remission for two years or more...The addition of IL18 did not result in any new or unexpected safety concerns beyond the known side effects of CAR T cell therapy, including cytokine release syndrome (CRS) and neurotoxicity, which were managed successfully. The researchers also found that the type of CAR T cell therapy patients previously received may impact the efficacy of huCART19-IL18...The research team already has several other clinical trials planned, including studies that will expand huCART19-IL18 to patients with acute lymphocytic leukemia (ALL) and chronic lymphocytic leukemia (CLL)."

New trial • P1 data • Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Hematological Malignancies • Non-Hodgkin’s Lymphoma

SAFETY AND EFFICACY OF ARMORED HUCART19-IL18 IN PATIENTS WITH RELAPSED/REFRACTORY LYMPHOMAS WHO PROGRESSED AFTER ANTI-CD19 CAR T-CELL THERAPY. (EHA 2024) - P1 | "Treatment with huCART19-IL18 has an acceptable safety profile and produced durable remissions in heavilypre-treated pts with R/R NHL despite prior CAR T-cell therapy. The subtype of the preceding CAR product mayinfluence the expansion and effectiveness of huCART19-IL18."

CAR T-Cell Therapy • Clinical • Diffuse Large B Cell Lymphoma • Fatigue • Hematological Malignancies • Hypotension • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • IL18

ASCO: New ‘Armored’ CAR produces significant responses in patients whose cancers don't respond to current CAR T cell therapies (Penn Medicine) - P1 | N=72 | NCT04684563 | "According to the results of a Phase I clinical trial, presented today at the American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract 7004), the new CAR T was safe, and had a three-month overall response rate of 80 percent in 20 patients with NHL whose cancers were relapsed or had stopped responding to treatment after receiving a commercially available CAR T cell therapy...The first-in-human study evaluated huCART19-IL18, an anti-CD19 CAR that was further modified to secrete the pro-inflammatory cytokine, interleukin 18 (IL 18), based on preclinical studies that showed it could enhance CAR T activity....As patient follow-up continues, the median overall survival after treatment has not been determined yet, with some of the earliest patients treated now in remission for two years or more."

P1 data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

TmCD19-IL18 in CD19+ Cancers (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: University of Pennsylvania | Not yet recruiting ➔ Recruiting

CAR T-Cell Therapy • Enrollment open • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ALK • BCL2 • BCL6 • CD19

TmCD19-IL18 in CD19+ Cancers (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: University of Pennsylvania

CAR T-Cell Therapy • New P1 trial • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ALK • BCL2 • BCL6 • CD19 • IGH • IL18

huCART19-IL18 Proves Safe and Elicits Durable Responses in CAR T–Pretreated R/R Lymphoma (OncLive) - P1 | N=72 | NCT04684563 | "No study-related deaths occurred with the fourth-generation CAR T-cell therapy, and no new safety signals were observed with IL-18. huCART19-IL18 elicited an objective response rate of 82% (95% CI, 53%-97%) in this population (n = 11), which included a complete response rate of 55% and a partial response rate of 27%. Eighteen percent of patients experienced disease progression. The median duration of response was not yet reached (NR; range, 6.6-NR). Moreover, the 12-month progression-free survival rate was 54% (95% CI, 15%-81%). At a median follow-up of 12 months (range, 3-20), the 12-month overall survival (OS) rate was 100%."

P1 data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology