Figure 1 from Safety and Tolerability of Letetresgene Autoleucel (GSK3377794): Pilot Studies in Patients with Advanced Non–Small Cell Lung Cancer

figure

posted on 2025-02-03, 08:21 authored by Mehmet Altan, Gilberto Lopes, T. Jeroen N. Hiltermann, Ramaswamy Govindan, Liza C. Villaruz, Emiliano Calvo, Martin J. Edelman, Muhammad Furqan, Joel Neal, Enriqueta Felip, Jennifer W. Carlisle, John V. Heymach, Róisín Eilish O’Cearbhaill, Marjorie Zauderer, Michael Chisamore, Ellie Corigliano, Ioanna Eleftheriadou, Stefan Zajic, Ben Jenkins, Sophia Goodison, Sunil Suchindran, Natalia Ramos-Hernandez, Nidale Tarek, Adam J. Schoenfeld

Patient attrition and NY-ESO-1 and LAGE-1a expression profiles in the multiarm study. A, Patient attrition for multiarm study. A total of 1,698 patients in the multiarm study were screened and signed the informed consent form. Out of 13 dosed patients, six withdrew prior to meeting interventional phase completion criteria, per protocol. B, NY-ESO-1 IHC P-score distribution of screened NY-ESO-1–positive patients in the multiarm study. NY-ESO-1–positive protein expression was detected as a continuous variable with distribution between 10% and 100% expression. There were 62 patients whose tumors expressed NY-ESO-1 with a P score of ≥10%, 1+, 2+, and 3+, with each vertical bar representing a unique tumor sample depicted by contributing IHC intensity of 0+ in blue, 1+ in light blue, 2+ in light orange, and 3+ in orange (425 patients whose tumors expressed NY-ESO-1 <10%, 1+, 2+, and 3+ are not displayed). One patient (ID #61 in the figure) had two samples. C, NY-ESO-1 expression profile of dosed NY-ESO-1–positive patients in the multiarm study. The mITT population based on NY-ESO-1 IHC expression is individually represented in the vertical bars with the P-score broken down by contributing IHC intensity of 0+ in blue, 1+ in light blue, 2+ in light orange, and 3+ in orange. The patients are ordered by P score, which is indicated by the red line. NY-ESO-1–negative, LAGE-1a–positive patients in the mITT population not shown. D, LAGE-1a RNA expression distribution of all tested patients in the multiarm study. The plot of patients tested for LAGE-1a RT-PCR RNA expression, in which the red line indicates the cutoff = 4 ΔCT, with positive cases depicted in red and negative cases depicted in blue. Triangles represent all patients screened. The two patients dosed who were LAGE-1a–positive are distinguished in the figure with a red circle. Patients with “no expression” were imputed as having the lowest observable value divided by 3. The vertical axis is reversed (zero is higher); lower LAGE-1a score measured by RT-PCR represents higher expression levels. E, NY-ESO-1 and LAGE-1a prevalence. This is a bar chart displaying NY-ESO-1 and LAGE-1a prevalence. LAGE-1a testing was performed on tissue samples in reflex to NY-ESO-1–negative status for when tissue was available. Prevalence includes unique samples from the same patient. NE, not evaluable.

History

ARTICLE ABSTRACT

The study aims to evaluate the safety, tolerability, and antitumor response of letetresgene autoleucel (lete-cel), genetically modified autologous T cells expressing a T-cell receptor specific for New York esophageal squamous cell carcinoma 1 (NY-ESO-1)/LAGE-1a shared epitope, alone or in combination with pembrolizumab, in HLA-A*02–positive (HLA-A*02:01, HLA-A*02:05, and/or HLA-A*02:06) patients with NY-ESO-1– and/or LAGE-1a–positive non–small cell lung cancer. Study 208749 was a single-arm study of lete-cel alone. Study 208471 was a multiarm study of lete-cel alone or in combination with pembrolizumab in patients with advanced or recurrent non–small cell lung cancer. More than 2,500 patients were screened for target expression. In the multiarm study, 738 (45%) of 1,638 tested patients were HLA-A*02–positive. NY-ESO-1 and LAGE-1a testing was positive in 12% (62/525) and 4% (15/348) of tested patients, respectively. Forty-one patients positive for HLA-A*02 and antigen expression were screened in the single-arm study. Overall, 43 patients underwent leukapheresis and 18 received lete-cel across studies. Lete-cel demonstrated a manageable safety profile. No fatal treatment-related serious adverse events (AE) were reported in either study. Cytopenias and cytokine release syndrome were the most common treatment-emergent AEs. Combining pembrolizumab with lete-cel did not seem to increase toxicity over lete-cel alone. Limited antitumor activity was observed; one of 18 patients had a durable response persisting for 18 months. Pharmacokinetic data showed similar T-cell expansion in all patients. Extensive HLA-A*02 and antigen expression testing was performed to identify potential participants. Lete-cel was generally well tolerated and had no unexpected AEs. Antitumor activity was observed in a limited number of patients.