Announcement • Jun 13
Lyell Immunopharma Presents Updated Safety Data And Translational Insights For Rondecabtagene Autoleucel In Patients With Large B-Cell Lymphoma Lyell Immunopharma, Inc. announced new safety data from the ongoing Phase 1/2 clinical trial of rondecabtagene autoleucel (ronde-cel) in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) in the second-line (2L) and third- and later-line (3L+) settings and new translational data for ronde-cel. More than 100 patients were treated with ronde-cel in 2L and 3L+ LBCL, with a manufacturing success rate of 97%. No Grade = 3 CRS and low rates of Grade = 3 ICANS were reported, supporting outpatient administration. 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. The population reflected high-risk disease: median age 64 years (range, 20 to 87), 67% (72/108) with primary refractory disease, and 28% (30/108) had an International Prognostic Index score of 3 or 4. Of the patients treated, 59% (64/108) received dexamethasone prophylaxis, 10 mg daily for three days at the time of CAR T-cell administration. 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. With over 100 patients treated, ronde-cel continues to show a consistent and manageable safety profile, supporting the potential for outpatient administration. Dexamethasone prophylaxis did not change ronde-cel cell expansion and pharmacokinetics. Manufacturing has also proven reliable to date, with a 97% success rate across these patients. Single-cell RNA sequencing was conducted on ronde-cel infusion products to assess memory potential of cytotoxic effector cells compared to FDA-approved CD19 CAR T-cell therapies. Cluster analysis identified a population of cytotoxic effector cells (defined by high GZMB, IFNG, CCL4, CCL5, KLRD1 gene expression) that had higher expression of memory-associated genes (CD62L, IL7R, LEF1) compared to an analogous cytotoxic cluster from FDA-approved CD19 CAR T-cell therapies. These cells co-expressing cytotoxic genes and memory-associated genes are referred to as Cytotoxic T cells with Memory Potential (Tcmp) in this study. 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. Ronde-cel is currently being evaluated for the treatment of R/R LBCL across two pivotal clinical trials. 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 the second half of 2027. In the 2L setting, the Phase 3 randomized PiNACLE-H2H trial is evaluating ronde-cel against investigator’s choice of axicabtagene ciloleucel or lisocabtagene maraleucel. Announcement • Jun 10
Lyell Immunopharma Provides Update on Safety Profile of Lyl273 and Amends Phase 1 Trial to Phase 1/2 Expansion Lyell Immunopharma provided an update on the safety profile of LYL273 in its ongoing U.S. Phase 1 clinical trial in patients with relapsed or refractory metastatic colorectal cancer (mCRC), and announced the Phase 1 trial has been amended to enable seamless expansion into a potential pivotal single-arm Phase 2 trial pending regulatory alignment. LYL273 is a guanylyl cyclase C (GCC)-targeted CAR T-cell product candidate enhanced with CD19 CAR expression and controlled cytokine release designed to improve CAR T-cell expansion, immune cell infiltration and cancer cell killing in the hostile solid tumor microenvironment. A 50% overall response rate across Dose Levels 1 and 2 has been previously reported (data cutoff date of October 28, 2025) in third- or later-line (3L+) relapsed or refractory mCRC patients in the U.S. Phase 1 clinical trial. The FDA has granted LYL273 Fast Track designation for the treatment of mCRC. Nineteen patients have been enrolled in the U.S. Phase 1 clinical trial across Dose Levels 1 and 2 (1 and 2 x 106 CAR+ cells/kg) as of the data cutoff date of May 5, 2026. Ten of these patients were enrolled under the new gastrointestinal (GI) prophylaxis regimen including infliximab, vedolizumab and budesonide, along with a standardized safety management plan. The GI prophylaxis and standardized safety management plan reduced Grade > 2 diarrhea or colitis from 55% to 10% in patients without (N = 9) and with (N = 10) GI prophylaxis, respectively. These ten patients did not experience Grade = 3 cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). No additional adverse events of interest have been identified. There was no difference observed in GCC-CAR+ cell expansion either in terms of maximum cell expansion or area under the curve in those patients who received GI prophylaxis and those who did not. Dose escalation continues in the U.S. Phase 1 clinical trial; the maximum tolerated dose has not been determined. The U.S. Phase 1 clinical trial evaluating LYL273 in relapsed or refractory 3L+ mCRC has been amended to a Phase 1/2 design (CARABINER). The amended design enables seamless expansion into a potential pivotal single-arm Phase 2 trial once the recommended Phase 2 dose has been determined, subject to discussions with the U.S. Food and Drug Administration (FDA). New centers are being added to the trial in preparation for initiating the dose expansion portion of the Phase 1/2 trial. The Phase 1 portion of the clinical trial includes four dose-escalation cohorts at Dose Levels 1 through 4 (1, 2, 3, 4 x 106 CAR+ cells/kg). Each dose-escalation cohort is designed to include three or six patients, with up to twenty-four patients across the four dose-escalation cohorts. In addition to the existing 3L+ cohorts, the amendment adds new cohorts, including a second-line cohort and a cohort evaluating a combination strategy with radiotherapy. Up to sixty patients are expected to be enrolled across the new cohorts. The Phase 2 portion will expand enrollment at the recommended Phase 2 dose in an open-label, single-arm cohort. In the second half of 2026, additional Phase 1 clinical data, including clinical outcomes, and an End-of-Phase 1 meeting with the FDA are expected. 
