rondecabtagene autoleucel (LYL314) / Lyell Immunopharma - LARVOL DELTA

Rondecabtagene Autoleucel, a Dual-Targeting CD19/CD20 CAR T-Cell Product, Exhibits a Manageable Safety Profile With Low Rates of Grade ≥3 CRS and ICANS in Relapsed/Refractory Large B-Cell Lymphoma (SOHO 2026) - P1/2 | " Patients with relapsed/refractory (R/R) LBCL (N = 87) were enrolled in a phase 1/2 trial (NCT05826535) evaluating ronde-cel following lymphodepletion with fludarabine and cyclophosphamide...Tocilizumab was administered in 35% of patients... Ronde-cel demonstrated a consistent and manageable safety profile in a broad population with R/R LBCL. The absence of grade ≥3 CRS and low rates of grade ≥3 ICANS and infection support the feasibility of ronde-cel administration in the outpatient setting. 2L: second-line, 3L+: third-line or higher, CD: cluster of differentiation."

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

The PiNACLE pivotal single-arm trial is ongoing, with additional data expected in the second half of 2026, pivotal data expected in mid-2027 and submission of a BLA to the FDA expected to follow in the second half of 2027 (The Manila Times)

FDA filing • P1/2 data • Large B Cell Lymphoma

PiNACLE-H2H, the first-of-its-kind Phase 3 randomized controlled trial evaluating ronde-cel versus investigator’s choice of axicabtagene ciloleucel or lisocabtagene maraleucel in patients with R/R LBCL in the 2L setting, continues to enroll patients. (The Manila Times) - "A progress update for this trial is expected in the second half of 2026."

Enrollment status • Trial status • Large B Cell Lymphoma

DURABLE RESPONSES WITH RONDECABTAGENE AUTOLEUCEL (DUAL-TARGETING CD19/CD20 CAR T-CELLS) ARE ASSOCIATED WITH HIGHER PROPORTION OF CYTOTOXIC T CELLS WITH MEMORY POTENTIAL IN INFUSION PRODUCTS (EHA 2026) - "P atients with a higher proportion of T cmp cells were more likely to achieve durable responses (≥12 months CR ). These findings support the hypothesis of an association between ronde- cel's durability of response and CD62L enrichment during manufacturing ."

CAR T-Cell Therapy • Hematological Malignancies • Lymphoma • Oncology • BACH2 • CCL3 • CD8 • GZMB • IFNG • IL7R

LOW-GRADE CRS AND ICANS WITH RONDECABTAGENE AUTOLEUCEL, A DUAL-TARGETING CD19/CD20 CAR T-CELL PRODUCT CANDIDATE, IN PATIENTS WITH LARGE B-CELL LYMPHOMA: UPDATED SAFETY ANALYSIS (EHA 2026) - P1/2 | "Methods Patients with R/R LBCL (N = 87) received ronde-cel following lymphodepletion with fludarabine and cyclophosphamide...Tocilizumab was administered in 35% (29/84) of patients...No Grade ≥ 3 CRS was observed, and <5% of patients reported with Grade ≥ 3 ICANS after the introduction of dexamethasone prophylaxis. These findings support the feasibility of clinical management of ronde-cel across a broad range of treatment settings for LBCL, including outpatient administration."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • IL6

Durable Responses with Rondecabtagene Autoleucel (Dual-Targeting CD19/CD20 CAR T-Cells) Are Associated with Higher Proportion of Cytotoxic T Cells with Memory Potential in Infusion Products (Poster: PF1097) (GlobeNewswire) - "Tcmp cells were more abundant in the ronde-cel products of patients with durable responses (>12 months) than in patients with progressive disease; Ronde-cel drug product Tcmp cells have a stronger memory potential compared to axicabtagene ciloleucel’s cytotoxic effector cells; Ronde-cel Tcmp cells following CD62L enrichment also had higher survival and expansion in vitro compared to cytotoxic effector cells with CD4/CD8 enrichment; Ronde-cel CAR+ T cells collected from patients two months after infusion sustained the capacity to proliferate, kill tumor cells, and secrete cytokines; Durable complete responses > 12 months observed in patients with LBCL with low CD19 or CD20 antigen expression on tumor biopsies at baseline."

P1/2 data • Large B Cell Lymphoma

Low-Grade CRS and ICANS with Rondecabtagene Autoleucel, a Dual-Targeting CD19/CD20 CAR T-Cell Product Candidate, in Patients with Large B-Cell Lymphoma: Updated Safety Analysis (Poster: PF962) (GlobeNewswire) - "A total of 108 patients with R/R LBCL (43 2L and 65 3L+) were treated with ronde-cel in the ongoing Phase 1/2 trial as of the data cutoff date of May 5, 2026...Cytokine Release Syndrome (CRS): There were no reports of Grade ≥ 3 events in patients treated with or without dexamethasone prophylaxis. Grade 1 CRS events were reported in 56% (36/64) and Grade 2 in 13% (8/64) of patients receiving prophylaxis, compared with cases of Grade 1 CRS reported in 30% (13/44) or Grade 2 in 39% (17/44) of patients who did not receive prophylaxis; Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): Grade ≥ 3 events of ICANS occurred in 8% (5/64) of patients receiving prophylaxis vs. 16% (7/44) of patients who did not receive prophylaxis. Grade 1 events were reported in 6% (4/64) and Grade 2 in 2% (1/64) of patients receiving prophylaxis vs. 11% (5/44) or 5% (2/44) who did not receive prophylaxis."

Cytokine release syndrome • P1/2 data • Large B Cell Lymphoma

In the 3L+ setting, the ongoing single-arm PiNACLE trial is expected to report updated data in the second half of 2026 and pivotal data by mid-2027, setting up a subsequent Biologics License Application (BLA) submission in 2027 (GlobeNewswire)

FDA filing • P1/2 data • Large B Cell Lymphoma

Lyell Immunopharma…announced that the Company will present data from its ongoing Phase 1/2 clinical trial of rondecabtagene autoleucel (ronde-cel) in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) at the European Hematology Association (EHA) 2026 Congress… (GlobeNewswire) - "The data will be featured in two poster presentations covering an updated ronde-cel safety analysis and translational insights."

P1/2 data • Large B Cell Lymphoma

Lyell Immunopharma Announces Closing of Additional $50 Million Tranche of Equity Private Placement… (GlobeNewswire) - "Lyell Immunopharma, Inc...announced it has closed the sale of an additional $50 million of shares of its common stock to investors from its July 2025 equity private placement of up to $100 million, following achievement of a clinical milestone within its PiNACLE pivotal trial evaluating rondecabtagene autoleucel (ronde-cel) in patients with relapsed/refractory large B-cell lymphoma (LBCL) in the third- or later-line setting."

Financing • Large B Cell Lymphoma

Lyell Immunopharma Announces Initiation of Patient Dosing in First-of-Its-Kind Phase 3 Head-To-Head CAR T-Cell Clinical Trial in Aggressive Large B-Cell Lymphoma (GlobeNewswire) - "PiNACLE - H2H is a Phase 3 head-to-head CAR T-cell randomized controlled clinical trial of ronde-cel versus Investigator’s choice of either liso-cel or axi-cel in patients with R/R LBCL receiving treatment in the 2L setting....Site activation for both PiNACLE - H2H and PiNACLE are underway in the United States, Canada and Australia....The pivotal single-arm trial, PiNACLE, evaluating ronde-cel in the third- or later-line setting is ongoing with BLA submission expected in 2027."

FDA filing • Trial status • Large B Cell Lymphoma

Rondecabtagene autoleucel, an autologous, dual-targeting CD19/CD20 CAR T-cell candidate manufactured from CD62L+ enriched T cells, achieves durable responses in patients with large B-cell lymphoma (ASH 2025) - P1/2 | "Following a standard 3-day LD regimen of fludarabine and cyclophosphamide, patients received a single dose of ronde-cel, in the outpatient or inpatient setting, at the recommended Phase 2 dose (RP2D) of 100 x 106 CAR cells...Grade 1 or 2 cytokine release syndrome (CRS) was reported in 62% (37/60) patients, with no ≥ Grade 3 CRS, and 42% (25/60) of all patients receiving tocilizumab...Grade ≥ 3 ICANS was reported in 13% (8/60) of patients, including 7% (1/15) of patients after the Introduction of routine dexamethasone prophylaxis, and resolved promptly with standard therapy (median time to < Grade 3 was 2.5 days)... Ronde-cel achieved high overall response and complete response rates with an encouraging safety profile in high-risk patients with LBCL in a Phase 1/2 multi-center trial. Complete responses were durable, including 100% CR at ≥ 6 months among patients treated in the 2L setting. A single-arm pivotal trial of ronde-cel is ongoing in patients treated in..."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma

CD62L enrichment achieves robust expansion and memory phenotype post-infusion in patients with LBCL treated with rondecabtagene autoleucel, an autologous, dual-targeting CD19/CD20 CAR T-cell candidate (ASH 2025) - P1/2 | "Rondecabtagene autoleucel (ronde-cel, LYL314) is an autologous, dual-targeting CD19/CD20 CAR T-cell therapy product candidate manufactured from CD62L+ enriched cells... Ronde-cel manufactured after CD62L enrichment resulted in increased stem-like and effector-memory properties in the infusion product compared to FDA approved CD19 CAR T-cell therapies in LBCL. These properties are positively correlated with robust expansion observed in patients and a high memory phenotype post infusion. These findings support the potential of ronde-cel to achieve improved clinical outcomes through enhanced product characteristics."

CAR T-Cell Therapy • Clinical • IO biomarker • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • CCR7 • CD8 • IL7R • LAG3 • TIGIT

PiNACLE-H2H: A Study to Investigate Ronde-cel Versus Investigator's Choice CD19 CAR T-Cell Therapy (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Lyell Immunopharma, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Ronde-cel Translational Data (GlobeNewswire) - "Translational data from the ongoing Phase 1/2 clinical trial showed that ronde-cel manufactured with CD62L enrichment achieved robust expansion and high expression of memory-related genes after infusion in patients with LBCL. An evaluation of ronde-cel and published data for CD19 CAR T-cell products demonstrated that ronde-cel had a higher proportion of CD62L-positive T cells with a higher proportion of memory-cell phenotype prior to infusion (ronde-cel, N = 34; axi-cel, N = 110 and tisagenlecleucel (tisa-cel), N = 31)."

Biomarker • P1/2 data • Large B Cell Lymphoma

Lyell Immunopharma Presents New Clinical Data from Ongoing Trial of Ronde-Cel Showing High Rates of Durable Complete Responses in Patients with Large B-cell Lymphoma at the 67th ASH Annual Meeting and Exposition (GlobeNewswire) - "As of the data cutoff date of September 5, 2025, ronde-cel continued to demonstrate robust clinical responses with a manageable safety profile appropriate for outpatient administration. A 93% overall response rate, a 76% complete response rate, and median progression-free survival of 18 months were reported for patients with relapsed and/or refractory (R/R) LBCL in the third- or later-line (3L+) setting. Patients evaluated in the second-line (2L) setting (94% with difficult-to-treat primary refractory disease) achieved an 83% overall response rate and a 61% complete response rate, and 70% of patients with a complete response remained in complete response at 6 months or longer."

P1/2 data • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Primary Mediastinal Large B-Cell Lymphoma

A CD19/CD20-Directed Bispecific CAR-T Cell Therapy in Relapsed or Refractory Aggressive B-Cell Non-Hodgkin Lymphoma (NHL) (ASH 2023) - P1, P1/2 | "The primary objective of Phase 2 is to estimate the efficacy of IMPT-314 as measured by CR rate. Secondary endpoints include evaluation of pharmacokinetics and time to event outcomes."

CAR T-Cell Therapy • IO biomarker • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • CD20 • CD8

PiNACLE - H2H is a Phase 3 head-to-head CAR T-cell therapy trial, which will evaluate ronde-cel versus an investigator’s choice of approved CD19 CAR T-cell therapies (lisocabtagene maraleucel or axicabtagene ciloleucel) in patients with aggressive LBCL receiving treatment in the 2L setting (GlobeNewswire) - "The trial is expected to enroll approximately 400 patients with R/R LBCL (200 per arm)....Clinical site initiation is underway for PiNACLE - H2H in the United States, Canada and Australia, and the first patient is expected to be enrolled by early 2026."

Trial status • Large B Cell Lymphoma

Data from…PiNACLE…trial are expected to form the basis of a Biologics License Application submission to the FDA in 2027 for patients with R/R LBCL receiving treatment in the 3L+ setting (GlobeNewswire)

FDA filing • Large B Cell Lymphoma

First Results of IMPT-314, an Autologous Bispecific CD19/CD20 Chimeric Antigen Receptor (CAR) in Enriched Naive and Central Memory T Cells, for the Treatment of Large B Cell Lymphoma (LBCL) (ASH 2024) - P1, P1/2 | "Conclusions : Initial results of IMPT-314 suggest a manageable tolerability profile, robust expansion, cellular persistence, and high rates of complete response in R/R, CAR T-naive LBCL. Additional results will be presented at the meeting."

B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Hematological Malignancies • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Rondecabtagene Autoleucel, an Autologous, Dual-Targeting CD19/CD20 CAR T-Cell Candidate Manufactured from CD62L+ Enriched T Cells, Achieves Durable Responses in Patients with Large B-Cell Lymphoma (GlobeNewswire) - "Lyell Immunopharma...announced...new clinical and translational data...will be presented at the 67th American Society of Hematology (ASH) Annual Meeting....The presentation will highlight new clinical data from the ongoing Phase 1/2 trial of ronde-cel in patients with LBCL. As of the abstract’s June 27, 2025 data cut-off date, high-risk patients with LBCL treated with ronde-cel achieved high overall response rates and complete response rates with an encouraging safety profile. New safety and efficacy data from patients receiving treatment in both the second-line and the third- or later-line settings will be presented."

P1/2 data • Large B Cell Lymphoma

CD62L Enrichment Achieves Robust Expansion and Memory Phenotype Post-Infusion in Patients with LBCL Treated with Rondecabtagene Autoleucel, an Autologous, Dual-Targeting CD19/CD20 CAR T-Cell Candidate (GlobeNewswire) - "Lyell Immunopharma...announced...new clinical and translational data...will be presented at the 67th American Society of Hematology (ASH) Annual Meeting....This presentation will review translational data from the ongoing Phase 1/2 clinical trial in patients receiving treatment in the second or third- or later-line settings, highlighting that CD62L-positive cell enrichment achieves greater memory phenotype expression and in vivo cell expansion compared to published data from U.S. Food and Drug Administration-approved CAR T-cell therapies for LBCL."

P1/2 data • Large B Cell Lymphoma

MPCT-012L: Study of LYL314 in Aggressive Large B-Cell Lymphoma (clinicaltrials.gov) - P1/2 | N=270 | Recruiting | Sponsor: Lyell Immunopharma, Inc. | Trial completion date: Jan 2028 ➔ Jun 2031 | Trial primary completion date: Aug 2026 ➔ Dec 2028

Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Follicular Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6

PiNACLE-H2H: A Study to Investigate Ronde-cel Versus Investigator's Choice CD19 CAR T-Cell Therapy (clinicaltrials.gov) - P3 | N=400 | Not yet recruiting | Sponsor: Lyell Immunopharma, Inc.

New P3 trial • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Lyell Immunopharma Announces the Initiation of a Phase 3 Head-to-Head CAR T-Cell Therapy Clinical Trial in Aggressive Large B-Cell Lymphoma… (GlobeNewswire) - "The trial is evaluating rondecabtagene autoleucel (ronde-cel, also known as LYL314) compared to lisocabtagene maraleucel (liso-cel) or axicabtagene ciloleucel (axi-cel) for the treatment of patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) receiving treatment in the 2L setting....Clinical site initiation is underway in the United States and Australia, and the first patient is expected to be enrolled by early 2026."

New P3 trial • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Primary Mediastinal Large B-Cell Lymphoma