rondecabtagene autoleucel (LYL314) / Lyell Immunopharma - LARVOL DELTA

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

Second Quarter Updates and Recent Business Highlights (GlobeNewswire) - "Data from...the PiNACLE...trial is 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."

FDA filing • Large B Cell Lymphoma

Lyell Immunopharma Reports Business Highlights and Financial Results for the Second Quarter 2025 (GlobeNewswire) - "An update on the progress of the PiNACLE trial is planned for late 2025....More mature data from the ongoing Phase 1/2 trial in the 2L setting are expected to be presented in late 2025....A Phase 3 randomized controlled trial of LYL314 is expected to be initiated by early 2026 in patients receiving treatment in the 2L setting with R/R LBCL."

New P3 trial • P1/2 data • Large B Cell Lymphoma • Non-Hodgkin’s Lymphoma

LYL314, A CD19/CD20 CAR T-CELL CANDIDATE ENRICHED FOR CD62L+ STEM-LIKE CELLS, ACHIEVES HIGH RATES OF DURABLE COMPLETE RESPONSES IN R/R LARGE B-CELL LYMPHOMA (ICML 2025) - P1/2 | "Following a standard lymphodepletion regimen of fludarabine and cyclophosphamide, patients received a single dose of LYL314... A high overall response rate (94%) and complete response rate (74%) with a manageable safety profile were achieved with LYL314 in patients with R/R LBCL in an ongoing Phase 1/2 multi-center trial. Complete responses were durable at 6 months (76%). A pivotal trial of LYL314 is ongoing in patients treated in the 3L+ setting without prior CAR T-cell exposure (PiNACLE Trial)."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20

Lyell Immunopharma Announces Positive New Clinical Data Demonstrating High Rates of Durable Complete Responses from the Phase 1/2 Trial of LYL314 for the Treatment of Aggressive Large B-cell Lymphoma (GlobeNewswire) - P1/2 | N=270 | NCT05826535 | Sponsor: Lyell Immunopharma, Inc. | "Lyell Immunopharma, Inc...announced positive new clinical data from the multi-center Phase 1/2 trial of LYL314, including data from patients with large B-cell lymphoma (LBCL) treated in the third- or later-line (3L+) setting....In efficacy-evaluable 3L+ patients, with a median follow up of 9 months (N = 25): The overall response rate was 88% (22/25 patients), with 72% (18/25) of patients achieving a complete response; 71% (10/14) of patients with complete response remained in complete response at ≥ 6 months; In initial data from efficacy-evaluable 2L patients, with a median follow up of 5 months (N = 11): The overall response rate was 91% (10/11 patients), with 64% (7/11) achieving a complete response; 100% (7/7) of patients with complete response were in complete response at last assessment, including 3/3 at ≥ 6 months."

P1/2 data • Large B Cell Lymphoma • Non-Hodgkin’s Lymphoma

Lyell Immunopharma Reports Business Highlights and Financial Results for the First Quarter 2025 (GlobeNewswire) - "First Quarter Updates and Recent Business Highlights:...(i) LYL314 clinical supply is now manufactured at the LyFE Manufacturing Center in Bothell, Washington following successful technology transfer and clearance by the FDA of an IND amendment....; (ii) A pivotal trial in the third- or later-line setting is expected to be initiated in mid-2025 in patients with relapsed and/or refractory LBCL who have not previously received CAR T-cell therapy; (iii) More mature data from the ongoing Phase 1/2 trial in the second-line setting are expected to be presented in late-2025; (iv) A pivotal trial in the second-line setting is expected to be initiated by early 2026 in patients with relapsed and/or refractory LBCL who have not previously received CAR T-cell therapy."

Commercial • New trial • P1/2 data • Large B Cell Lymphoma

Lyell Immunopharma Announces Oral Presentation of New Clinical Data from the Phase 1/2 Trial of LYL314 for the Treatment of Large B-cell Lymphoma at the International Conference on Malignant Lymphoma (ICML) 2025 (GlobeNewswire) - "Lyell Immunopharma...announced that an abstract highlighting new clinical data from the Phase 1/2 trial of LYL314 (formerly IMPT-314) in large B-cell lymphoma will be presented as an oral presentation at the International Conference on Malignant Lymphoma (ICML) 2025....Details of the presentation are below: LYL314, a CD19/CD20 CAR T-cell candidate enriched for CD62L+ stem-like cells, achieves high rates of durable complete responses in R/R large B-cell lymphoma...; Presentation Date & Time: June 18, 2025, 5:40 pm CEST (11:40 am ET)....Presentation Number: 106."

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. | N=150 ➔ 270 | Trial completion date: Dec 2029 ➔ Jan 2028 | Trial primary completion date: Jun 2025 ➔ Aug 2026

Enrollment change • 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

Lyell Immunopharma Receives Regenerative Medicine Advanced Therapy (RMAT) Designation for LYL314 for the Treatment of Relapsed and/or Refractory Large B-Cell Lymphoma (GlobeNewswire) - "Lyell Immunopharma...announced that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to LYL314 (formerly IMPT-314) for the treatment of adult patients with relapsed and/or refractory large B-cell lymphoma after two or more prior lines of therapy. LYL314 is a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of response as compared to the approved CD19‑targeted CAR T-cell therapies for the treatment of aggressive large B-cell lymphoma (LBCL)....'The RMAT designation for LYL314, is based on promising clinical data from our ongoing Phase 1/2 trial...'"

FDA event • Large B Cell Lymphoma

Lyell Immunopharma Reports Business Highlights and Financial Results for the Fourth Quarter and Full Year 2024 (GlobeNewswire) - "Fourth Quarter Updates and Recent Business Highlights:...IMPT-314:...More mature data from the ongoing Phase 1/2 trial in the 3rd line+ setting and initial data from patients in the 2nd line setting are expected to be presented in mid-2025. Pivotal trial in the 3rd line+ setting is expected to be initiated in mid-2025 in patients with relapsed/refractory aggressive LBCL who have not previously received CAR T-cell therapy. Pivotal trial in the 2nd line setting expected to be initiated by early 2026 in patients with relapsed/refractory aggressive LBCL who have not previously received CAR T-cell therapy."

New trial • P1/2 data • Large B Cell Lymphoma

Lyell to Highlight Vision for its Next-Generation CAR T-Cell Therapy Pipeline at 43rd Annual JP Morgan Healthcare Conference (GlobeNewswire) - "Upcoming Milestones and Financial Outlook...For IMPT-314, a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate for the treatment of large B-cell lymphoma: Present data from the ongoing Phase 1-2 trial in mid-2025, including more mature data from the 3rd line+ cohort and initial data from the 2nd line cohort; Present more mature clinical data from the 2nd line cohort in late 2025 Initiate a pivotal trial in the 3rd line+ setting in mid-2025; Initiate a pivotal trial in the 2nd line setting by early 2026...For early-stage solid tumor programs: Submit first IND application for a new solid tumor CAR T-cell product candidate in 2026....Lyell expects net cash use in 2025 to be $175 million - $185 million, which extends its cash runway further into 2027 through multiple clinical milestones."

Commercial • IND • New trial • P1/2 data • 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

Lyell Presents Positive Initial Clinical Data from the Phase 1-2 Clinical Trial of IMPT-314 for the Treatment of B-cell Lymphoma at the 2024 ASH Annual Meeting (GlobeNewswire) - P1/2 | N=150 | NCT05826535 | Sponsor: ImmPACT Bio | "As of October 22, 2024 (the data cutoff for the presentation), 23 patients with relapsed or refractory (R/R), CAR T-naive large B-cell lymphoma received IMPT-314. The efficacy evaluable population consisted of 17 patients. The ORR was 94% (16/17 patients), with 71% (12/17 patients) achieving a CR by three months. The median follow up was 6.3 months (range 1.2 – 12.5 months) and 71% of patients were in response at last follow-up). In the safety evaluable population of 23 patients, no Grade 3+ CRS was reported. Grade 3 ICANS was reported in 13% (3/23) of patients with a median time to complete ICANS resolution of 5 days, and rapid improvement to Grade 2 or lower with standard therapy."

P1/2 data • Non-Hodgkin’s Lymphoma

Lyell Announces Presentation of Initial Clinical Data from the Phase 1-2 Clinical Trial of IMPT-314 for the treatment of B-cell Lymphoma at the 2024 American Society of Hematology (ASH) Annual Meeting (GlobeNewswire) - "Details of the presentation are below: 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)....Publication Number: 4824....Presentation Date & Time: Monday, December 9, 2024, 6:00 PM - 8:00 PM."

P1 data • Diffuse Large B Cell Lymphoma • Non-Hodgkin’s Lymphoma

Lyell Immunopharma Completes Acquisition of ImmPACT Bio (GlobeNewswire) - "Lyell Immunopharma, Inc...announced today that it has completed its acquisition of ImmPACT Bio USA Inc...Lyell will accelerate the development of IMPT-314...for hematologic malignancies, including B-cell non-Hodgkin lymphoma....We are focused on accelerating the development of IMPT-314 for patients with aggressive B-cell non-Hodgkin lymphoma and look forward to presenting initial data from the Phase 1-2 trial of IMPT-314 in patients treated in the 3rd line CAR-naïve setting at a major medical conference later this year....As previously disclosed, following the closing of this acquisition, Lyell expects its cash balance will fund operations into 2027, through important clinical milestones for each pipeline program, including initiation of a pivotal trial for IMPT-314, which is expected to start in 2025."

M&A • New trial • P1/2 data • Hematological Malignancies • Non-Hodgkin’s Lymphoma

Lyell Immunopharma to Acquire ImmPACT Bio and Prioritizes its Pipeline to Focus on Next-Generation CAR T-cell Therapies (GlobeNewswire) - "Lyell Immunopharma...announced today that it has entered into a definitive agreement to acquire ImmPACT Bio USA....ImmPACT’s lead program, IMPT-314, is a CD19/20-targeting chimeric antigen receptor (CAR) T-cell product candidate that Lyell will continue to develop for hematologic malignancies....Upon closing, Lyell will acquire worldwide rights to ImmPACT’s pipeline, including the next- generation bispecific CD19/CD20 autologous CAR T-cell therapy...and an activating TGF-beta Claudin 18.2 CAR T-cell candidate, which is in preclinical development. Lyell will prioritize the development of IMPT-314 for patients with B-cell lymphoma....Data from ImmPACT’s multi-center Phase 1-2 clinical trial of IMPT-314 in patients with large B-cell lymphoma treated in the 3rd line CAR-naïve setting to be presented at a major medical conference later this year; initiation of a pivotal trial for IMPT-314 expected in 2025."

M&A • New trial • P1/2 data • Non-Hodgkin’s Lymphoma

MPCT-012L: Study of IMPT-314 in R/R Aggressive B-cell NHL (clinicaltrials.gov) - P1/2 | N=150 | Recruiting | Sponsor: ImmPACT Bio | N=100 ➔ 150

Enrollment change • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6

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 • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD20 • CD8

Study of IMPT-314 in R/R Aggressive B-cell (clinicaltrials.gov) - P1/2 | N=100 | Recruiting | Sponsor: ImmPACT Bio | N=50 ➔ 100

Enrollment change • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6

ImmPACT Bio Doses First Patient in Phase 1/2 Trial Evaluating IMPT-314, a Bispecific CD19/CD20 CAR T-cell Therapy for the Treatment of Aggressive B-cell Lymphoma (BioSpace) - "Sarah Larson...added, 'While CD19 CAR T-cell therapies have transformed the lymphoma treatment landscape, durability has been limited by treatment resistance due to selective pressure against the target antigen and subsequent loss of expression. We designed this therapy to target both CD19 and CD20 to help restrict antigen escape and ultimately prolong treatment response. We look forward to delineating the differentiated therapeutic potential of this bispecific approach through data from ImmPACT Bio's Phase 1/2 trial of IMPT-314.'"

Media quote • P1/2 data

ImmPACT Bio Doses First Patient in Phase 1/2 Trial Evaluating IMPT-314, a Bispecific CD19/CD20 CAR T-cell Therapy for the Treatment of Aggressive B-cell Lymphoma (PRNewswire) - "ImmPACT Bio USA...announced that the first patient has been dosed in the Phase 1/2 trial evaluating IMPT-314, a bispecific CD19/CD20 CAR T-cell therapy for the treatment of relapsed or refractory (R/R) aggressive B-cell lymphoma...'We expect to present Phase 1 safety and initial efficacy data from patients with relapsed or refractory aggressive B-cell lymphoma in the first half of 2024'....ImmPACT Bio's Phase 1/2 is a multi-center, open-label clinical trial that will evaluate the safety and efficacy of IMPT-314 in participants with R/R aggressive B-cell lymphoma. The dose-finding Phase 1 portion of the study will include both CAR T-experienced and CAR T-naïve patients."

P1/2 data • Trial status • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

ImmPACT Bio Granted FDA Fast Track Designation for IMPT-314 in Patients with Relapsed or Refractory Aggressive B-cell Lymphoma (Markets Insider) - "...In 2019, Sarah Larson, M.D...initiated an ongoing investigator-led Phase 1 study of IMPT-314 in patients with R/R non-Hodgkin lymphoma. ImmPACT Bio in-licensed the logic-gate-based CAR T-cell platforms from UCLA."

Study of IMPT-314 in R/R Aggressive B-cell (clinicaltrials.gov) - P1/2 | N=50 | Recruiting | Sponsor: ImmPACT Bio | Not yet recruiting ➔ Recruiting

Enrollment open • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6

ImmPACT Bio Granted FDA Fast Track Designation for IMPT-314 in Patients with Relapsed or Refractory Aggressive B-cell Lymphoma (PRNewswire) - P1 | N=11 | "In 2019, Sarah Larson, M.D., also at UCLA, initiated an ongoing investigator-led Phase 1 study of IMPT-314 in patients with R/R non-Hodgkin lymphoma....Key safety and efficacy highlights from the Phase 1 UCLA investigator-led study (n = 11): 91% objective response rate, with 73% achieving a durable complete response; 18.2 months median progression-free survival with a median follow-up of 20.5 months; No neurotoxicity or immune effector cell-associated neurotoxicity syndrome; No cytokine release syndrome above Grade 1."

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