Assessment of Safety and Recommended Phase 2 Dose of Autologous T Cells Engineered With an Affinity-enhanced TCR Targeting NY ESO 1 and LAGE 1a, and Co-expressing the dnTGF-βRII (GSK3845097) in Participants With NY ESO 1 and/or LAGE 1a Positive Previously Treated Advanced (Metastatic or Unresectable) Synovial Sarcoma and Myxoid/Round Cell Liposarcoma

To assess the safety, tolerability and determine recommended phase 2 dose (RP2D) of GSK3845097 in HLA-A*02:01, HLA-A*02:05 and/or HLA-A*02:06 positive participants with New York esophageal squamous cell carcinoma (NY-ESO)-1 and/or Cancer testis antigen 2 (LAGE-1a) positive, previously treated, advanced (metastatic or unresectable) Synovial Sarcoma (SS) and Myxoid/Round Cell Liposarcoma (MRCLS).

Start Date21 Dec 2020

Sponsor / Collaborator

Adaptimmune Ltd.

NCT04526509

/ TerminatedPhase 1

Master Protocol to Assess the Safety and Recommended Phase 2 Dose of Next Generations of Autologous Enhanced NY-ESO-1/ LAGE-1a TCR Engineered T-cells, Alone or in Combination With Other Agents, in Participants With Advanced Tumors

This trial will evaluate the safety and efficacy of first time in human engineered T-cell therapies, in participants with advanced tumors.

Start Date21 Dec 2020

Sponsor / Collaborator

Adaptimmune Ltd.

NCT03967223

/ Active, not recruitingPhase 2

Master Protocol to Assess the Safety and Antitumor Activity of Genetically Engineered NY-ESO-1-Specific (c259) T Cells, Alone or in Combination With Other Agents, in HLA-A2+ Participants With NY-ESO-1 and/or LAGE-1a Positive Solid Tumors (IGNYTE-ESO)

This trial will evaluate safety and efficacy of human engineered T-cell therapies, in participants with advanced tumors.

Start Date31 Dec 2019

Sponsor / Collaborator

Adaptimmune Ltd.

100 Clinical Results associated with LAGE-1a Positive Solid Tumors

100 Translational Medicine associated with LAGE-1a Positive Solid Tumors

0 Patents (Medical) associated with LAGE-1a Positive Solid Tumors

Literatures (Medical) associated with LAGE-1a Positive Solid Tumors

01 Apr 2025·Cell Reports Medicine

Phase 1 study of IMCnyeso, a T cell receptor bispecific ImmTAC targeting NY-ESO-1-expressing malignancies

Article

Author: Thistlethwaite, Fiona ; Butler, Marcus O ; Sato, Takami ; Lopez, Juanita S ; Arkenau, Hendrik-Tobias ; Wustner, Jason ; Edukulla, Ramakrishna ; Johnson, Melissa L ; D'Angelo, Sandra P ; Rodon, Jordi ; Milhem, Mohammed ; Van Tine, Brian A ; Marshall, Shannon

IMCnyeso, an immune mobilizing monoclonal T cell receptor against cancer (ImmTAC) bispecific (New York esophageal squamous cell carcinoma [NY-ESO]×CD3) T cell engager, targets an NY-ESO-1/L-antigen family member-1 isoform A (LAGE-1A) peptide presented by histocompatibility leukocyte antigen (HLA)-A∗02:01. In this phase 1 study, 28 HLA-A∗02:01+ patients with advanced NY-ESO-1/LAGE-1A-positive advanced tumors (n = 28) receive IMCnyeso weekly intravenously (dose range: 3-300 μg; 7 dose-escalation cohorts). The primary objective is to identify the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D); additional objectives include preliminary anti-tumor activity, pharmacokinetics, immunogenicity, and pharmacodynamic changes. The study was terminated before fully enrolling dose escalation, and the MTD was not identified. There are no treatment-related discontinuations or deaths. The most common adverse events are grade 1/2 cytokine release syndrome and associated symptoms. Cytokine induction and transient lymphocyte count decreases are observed at doses 30-300 μg. At these doses, preliminary efficacy includes mixed response (2 patients) and a median overall survival of 12 months. IMCnyeso is well tolerated and, at doses ≥30 μg, induces pharmacodynamic changes consistent with T cell redirection. This study was registered at ClinicalTrials.gov (NCT03515551).

11 Apr 2023·Blood Advances

Safety and efficacy of letetresgene autoleucel alone or with pembrolizumab for relapsed/refractory multiple myeloma

Article

Author: Zajic, Stefan ; Urbano, Alisa ; Rapoport, Aaron P. ; Eleftheriadou, Ioanna ; Chisamore, Michael ; Suchindran, Sunil ; Huff, Anne ; Hoffman, James E. ; D’Souza, Jimson W. ; Kapoor, Gurpreet S. ; Faitg, Thomas ; Nishihori, Taiga

AbstractThis pilot study assessed the safety and efficacy of letetresgene autoleucel (lete-cel; GSK3377794), a genetically modified autologous T-cell therapy targeting New York esophageal squamous cell carcinoma-1 (NY-ESO-1)/L antigen family member 1 isoform A (LAGE-1a)–positive myeloma cells, alone or in combination with pembrolizumab in patients with relapsed/refractory multiple myeloma. Eligible patients expressed NY-ESO-1 and/or LAGE-1a and either HLA-A∗02:01, ∗02:05, or ∗02:06. Patients received lete-cel single infusion alone (arm 1) or with pembrolizumab (arm 2). 127 patients were screened, and 6 patients (3 per arm) were enrolled; patients in arm 1 and 2 received lete-cel alone, or with pembrolizumab, respectively. All patients exhibited grade 3/4 cytopenias, which resolved or improved to grade 1. One patient (arm 1) had grade 3/4 lete-cel–related adverse events (AEs); 2 patients (arm 2) had grade 3/4 AEs related to lete-cel and lymphodepletion. Three patients with grade 1/2 cytokine release syndrome (CRS) exhibited elevated post–lete-cel interleukin-6 levels versus those without CRS. Pooled overall response rate was 50% including 1 patient each with confirmed clinical response, very good clinical response, and partial response, and progression-free survival ranged from 1.3 to 5.2 months. Responders (arm 1: n = 1; arm 2: n = 2) had a time-to-response of 3 weeks, duration of response of 2.1 months. Two responders, but no nonresponders, exhibited elevated cytokine levels after lete-cel infusion. Lete-cel had a manageable safety profile and demonstrated clear but transient antitumor activity in patients with relapsed/refractory multiple myeloma. This trial was registered at www.clinicaltrials.gov as #NCT03168438.

01 Apr 2013·Cancer Immunology, ImmunotherapyQ2 · MEDICINE

Bi-specific TCR-anti CD3 redirected T-cell targeting of NY-ESO-1- and LAGE-1-positive tumors

Q2 · MEDICINE

Article

Author: Milos Aleksic ; Michael Kalos ; Tereza Osdal ; Rebecca Ashfield ; Alex S. Powlesland ; Olivier Morteau ; Deborah H. Sutton ; Namir J. Hassan ; Annelise Vuidepot ; Bent K. Jakobsen ; Malkit Sami ; Akhil Kotian ; Deborah Baker ; Carl H. June ; Maja Mujić ; Bjørn Tore Gjertsen ; Nikolai M. Lissin ; Katherine J. Adams ; Emmet McCormack

NY-ESO-1 and LAGE-1 are cancer testis antigens with an ideal profile for tumor immunotherapy, combining up-regulation in many cancer types with highly restricted expression in normal tissues and sharing a common HLA-A*0201 epitope, 157-165. Here, we present data to describe the specificity and anti-tumor activity of a bifunctional ImmTAC, comprising a soluble, high-affinity T-cell receptor (TCR) specific for NY-ESO-1157-165 fused to an anti-CD3 scFv. This reagent, ImmTAC-NYE, is shown to kill HLA-A2, antigen-positive tumor cell lines, and freshly isolated HLA-A2- and LAGE-1-positive NSCLC cells. Employing time-domain optical imaging, we demonstrate in vivo targeting of fluorescently labelled high-affinity NYESO-specific TCRs to HLA-A2-, NY-ESO-1157-165-positive tumors in xenografted mice. In vivo ImmTAC-NYE efficacy was tested in a tumor model in which human lymphocytes were stably co-engrafted into NSG mice harboring tumor xenografts; efficacy was observed in both tumor prevention and established tumor models using a GFP fluorescence readout. Quantitative RT-PCR was used to analyze the expression of both NY-ESO-1 and LAGE-1 antigens in 15 normal tissues, 5 cancer cell lines, 10 NSCLC, and 10 ovarian cancer samples. Overall, LAGE-1 RNA was expressed at a greater frequency and at higher levels than NY-ESO-1 in the tumor samples. These data support the clinical utility of ImmTAC-NYE as an immunotherapeutic agent for a variety of cancers.

News (Medical) associated with LAGE-1a Positive Solid Tumors

11 Apr 2023

·www.fiercebiotech.com

GSK pays out £30M to Adaptimmune as cell therapy work officially wraps up

After much back and forth, GSK is handing Adaptimmune responsibility for two cell therapy programs and related trials. GSK is paying Adaptimmune 30 million pounds sterling ($37.3 million) to wipe its hands of two programs, one of which includes lete-cel, an asset the U.K. pharma at one point touted as its leading cell therapy. Last October, GSK axed its NY-ESO-1 T-cell receptor (TCR) pact for lete-cel with Lyell that was worth over $1 billion in biobucks, moving the program over to T-cell therapy-focused Adaptimmune, where lete-cel originated. Now, the Big Pharma is giving back all rights and materials related to the NY-ESO program to Adaptimmune, alongside a cell therapy program in preclinical development dubbed PRAME. Sponsorship for the midstage clinical trial IGNYTE-ESO will also be transferred back to Adaptimmune in the third quarter of this year. The phase 2 study is assessing lete-cel alongside two chemotherapies in patients with NY-ESO-1 and/or LAGE-1a positive solid tumors. The Big Pharma is also handing over responsibility for a related long-term follow-up trial. All other clinical trials tied to the NY-ESO program have already wrapped up enrollment and are completed or will be soon by GSK. For the trouble of transferring the clinical trials, GSK is doling out the 30 million pound payment to Adaptimmune, consisting of an upfront fee plus milestones. The first-gen candidate lete-cel was at one point GSK’s lead cell therapy candidate, though the Big Pharma appeared to reassess its broader work on NY-ESO-1 after lackluster data from a phase 1/2 non-small cell lung cancer trial prompted an early end to enrollment. After that, GSK ended its Lyell partnership, which aimed to use Lyell's tech to improve the depth and durability of clinical responses. The Big Pharma then gave the program back to Adaptimmune, a biotech that struck up a partnership with GSK in 2014. Back then, the companies agreed to look at up to five programs, with the first being NY-ESO, which GSK exclusively licensed three years later. The PRAME program also sprung from this collaboration. Adaptimmune plans to have the targeted TCR T-cell therapy ready for an IND submission later this year, which would allow the program to be assessed in human trials if approved by the FDA.

Cell TherapyPhase 2ImmunotherapyIND

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