Legend Biotech presented preliminary results from its ongoing Phase I/II trial of LB2102 (NCT05680922), an armoured delta-like ligand 3 (DLL3)-targeted autologous chimeric antigen receptor (CAR)-T cell therapy, in patients with relapsed or refractory (r/r) small cell lung cancer (SCLC) or large cell neuroendocrine carcinoma (LCNEC) at the American Society of Clinical Oncology 2026 Annual Meeting, held May 29–June 2, 2026. In the second-line setting, the current standard of care for extensive-stage (ES)-SCLC is Amgen’s Imdelltra (tarlatamab), a DLL3- and CD3-targeting bispecific T-cell engager. Legend Biotech has a more expansive inclusion criteria than Imdelltra’s pivotal DeLLphi-304 trial (NCT05740566) and included LCNEC patients alongside those with ES-SCLC. Patients who had previously received Imdelltra were ineligible. Novartis licensed this therapy from Legend Biotech and is expected to run a separate development program focusing on ES-SCLC patients, potentially enrolling patients with prior Imdelltra exposure.
In this trial, 20 patients were treated across the planned seven dose levels. CAR-T expansion was measurable in all patients who received dose level 3 or above (≥2.0×106 CAR-T cells/kg). The overall response rate (ORR) for patients receiving dose level 3 or above was 28.6% and the disease control rate (DCR) was 78.6%. For comparison, in DeLLphi-304, Imdelltra achieved an ORR of 35% and DCR of 68%. The median duration of response (mDOR) was 6.5 months versus Imdelltra’s achieved mDOR of 6.9 months in DeLLphi-304. Safety signals were moderate for an autologous CAR-T therapy, with cytokine release syndrome (CRS) occurring in six patients, all cases of which were grade 2 or below, and three patients experienced immune effector cell–mediated neurotoxicity syndrome (ICANS), one of which was grade 3.
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These efficacy results fall short of what Novartis would have hoped for, though context matters. When the presenter was questioned about the manufacturing process, he stated that vein-to-vein times were often 8–10 weeks. Patients would be receiving bridging chemotherapy during this time and considering that median progression-free survival for patients on the chemotherapy arm of the DeLLphi-304 trial was only 3.2 months, a significant proportion of patients will have already progressed between apheresis and dosing with the CAR-T cells. This may be one of the reasons that Novartis has decided to run a separate program, as its T-Charge manufacturing platform can produce autologous CAR-T cells within two days and could reduce vein-to-vein times to potentially under two weeks. With efficacy already comparable to Imdelltra, if that shorter vein-to-vein time can be achieved, LB2102 may compare favorably to Amgen’s Imdelltra when Novartis’s trial reads out. However, by the time LB2102 reaches pivotal trials, Imdelltra may no longer be the benchmark. Trispecific T-cell engagers with dual DLL3 epitope targeting are currently in development, such as Zelgen Biopharmaceutical’s alveltamig, which is currently in a pivotal trial in China (NCT07189455) and licensed to AbbVie for ex-China development. According to GlobalData’s analyst consensus forecast, LB2102 sales will reach $22 million in 2032. Novartis has a long way to go for the development of this asset to be worth the cost.
