CTAG1B expression

P2, N=7, Active, not recruiting, Adaptimmune | Trial completion date: Jul 2024 --> Jul 2025

P1, N=22, Active, not recruiting, University Health Network, Toronto | Trial completion date: Sep 2024 --> Sep 2025 | Trial primary completion date: Sep 2024 --> Sep 2025

P2, N=103, Active, not recruiting, Adaptimmune | Trial primary completion date: Nov 2022 --> Aug 2024

P1, N=18, Recruiting, TCRCure Biopharma Ltd. | Phase classification: P1/2 --> P1 | Trial primary completion date: Oct 2023 --> Oct 2024

P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2024 --> Mar 2025 | Trial primary completion date: Mar 2024 --> Mar 2025

These findings indicate that the HSP70/NY-ESO-1 p86-94 may significantly enhance CTLs-mediated cytotoxicity and targeting ability against NY-ESO-1-expressing tumors in vitro. 5-Aza-CdR treatment with HSP70 binding to tumor antigen is a new strategy for immunotherapy of the tumors with poor CTA expression.

No significant difference in NY-ESO-1 expression in primary tumors was observed concerning lymph node metastasis status. In summary, our findings suggest that increased expression of NY-ESO-1 could potentially serve as a prognostic biomarker for gastric cancer.

P1, N=22, Active, not recruiting, University Health Network, Toronto | Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Sep 2024

P1/2, N=8, Completed, Takara Bio Inc. | Active, not recruiting --> Completed

Hypomethylating agents like DAC upregulate immunogenic signatures in primary and immortalized GBM cells, rendering them susceptible to antigen specific T-cell targeting. These pleiotropic effects demonstrate strong preclinical rationale for use of DAC to sensitize GBM for targeting by immune therapies.

Previous work from our group has shown that Decitabine (DAC), a demethylating agent, can improve the immunogenicity of Glioblastoma (GBM) for immuno-therapeutic targeting through the upregulation of immunogenic cancer testis antigens (CTA) such as NY-ESO-1 and altered expression of other immunoregulatory programs... Our results demonstrate a preclinical rationale for the use of GSK as a viable pro-antigenic agent for the sensitization of GBM to targeted immune therapy.

P1, N=4, Active, not recruiting, Roswell Park Cancer Institute | Trial completion date: Sep 2023 --> Jan 2024

P2, N=28, Completed, National Cancer Institute (NCI) | Active, not recruiting --> Completed | Trial completion date: Apr 2024 --> Mar 2023

Adoptive immunotherapy with TBI-1301 to selectively target NY-ESO-1 positive tumor cells appears to be a promising strategy for the treatment of advanced or recurrent synovial sarcoma with acceptable toxicity.

Finally, MVny was able to induce DC maturation. Altogether, these results show that MVny could be an interesting candidate to stimulate NY-ESO-1-specific T cells in melanoma patients with NY-ESO-1-expressing tumor cells.

Enrolled patients receive TAEST16001 cell infusion after dose-reduced lymphodepletion with cyclophosphamide (15 mg/kg/day × 3 days) combined with fludarabine (20 mg/m/day × 3 days), and the TCR-T cells are maintained with low doses of interleukin-2 injection post-adoptive transfer. The median progression-free survival is 7.2 months, and the median duration of response is 13.1 months. The protocol of TAEST16001 cells delivers a safe and highly effective treatment for patients with advanced soft tissue sarcoma (ClinicalTrials.gov: NCT04318964).

P2, N=7, Active, not recruiting, GlaxoSmithKline

P1/2, N=16, Completed, Astellas Pharma Global Development, Inc. | Active, not recruiting --> Completed | N=339 --> 16 | Trial completion date: Jul 2024 --> May 2023 | Trial primary completion date: Jul 2024 --> May 2023

Trial design This is a multi-centre, first-in-human, phase I/IIa, randomised, open label trial, run in the UK, for patients scheduled to receive first-line chemo-immunotherapy containing pembrolizumab as standard of care (SoC) treatment, for Stage III/IV NSCLC (and potentially additional indications) expressing MAGE-A3 +/- NYESO-1 (NCT04908111)...The primary objective is safety and tolerability, with key secondary objectives of immunogenicity and clinical efficacy. Tertiary objectives include correlative translational analyses.

P2, N=28, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Apr 2023 --> Apr 2024

P1, N=4, Active, not recruiting, Roswell Park Cancer Institute | Trial completion date: Jun 2023 --> Sep 2023

Patients whose gallbladder cancer expresses NY-ESO1 or PD-L1 might be candidates for immunotherapy.

P1/2, N=18, Recruiting, TCRCure Biopharma Ltd.

ACT of NY-ESO-1 transgenic T cells given with DC vaccination and anti-PD-1 therapy resulted in transient antitumor activity. NY-ESO-1 expression was lost in the post-treatment sample in the setting of extensive methylation of the NY-ESO-1 promoter region.

TBI-1301 was infused at split dose of 5 x 109 cells following cyclophosphamide treatment at 750 mg/m2 for two days to HLA-A*02:01 or HLA-A*02:06 positive subjects with synovial sarcoma expressing NY-ESO-1, which were surgically unresectable and refractory to anthracycline therapy...All subjects who developed CRS recovered with prespecified treatment, in which 2 subjects were treated with symptomatic therapy, 1 subject was treated with tocilizumab and 1 subject was treated with both tocilizumab and corticosteroid... Adoptive immunotherapy with TBI-1301 to selectively target NY-ESO-1 positive tumors will become a promising treatment for advanced or recurrent synovial sarcoma with acceptable toxicity. Clinical trial information: NCT03250325.

P1, N=11, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed

P1/2, N=339, Active, not recruiting, Astellas Pharma Global Development, Inc. | Trial completion date: Jan 2028 --> Jul 2024 | Trial primary completion date: Jan 2026 --> Jul 2024

P1/2, N=75, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2023 --> Mar 2024 | Trial primary completion date: Mar 2023 --> Mar 2024

P1/2, N=339, Active, not recruiting, Astellas Pharma Global Development, Inc. | Recruiting --> Active, not recruiting

Combined administration with anti-PD-1 antibody, NY-ESO-1 S-FLU virus augmented the tumour protection by reducing the tumour metastasis. We propose that the antigen delivery through S-FLU is highly efficient in inducing antigen-specific CD8 T cell response and protection against tumour development in combination with PD-1 blockade.

Immunological correlates to the clinical development were the decrease of tumor-driven NY-ESO-1 serum antibody and the drop of prostate-specific antigen to <0.01 µg/L. TILs were reactive against cancer-testis antigen NY-ESO-1, individual tumor mutational proteins (eg, PRPF8, TRPS1), and the androgen receptor splice variant 12.

P1, N=22, Active, not recruiting, University Health Network, Toronto | Trial completion date: Sep 2022 --> Sep 2023 | Trial primary completion date: Sep 2022 --> Sep 2023 | Recruiting --> Active, not recruiting

The high expression of PRAME in TNBCs makes it a potential therapeutic target, while NY-ESO1 appears to be a less useful marker. However, further larger studies are needed to ascertain the utility of these markers.

Two responders, but none of the non-responders, exhibited elevated cytokine levels post lete-cel infusion. Lete-cel had a manageable safety profile consistent with other lete-cel studies and demonstrated clear but transient antitumor activity in patients with RRMM.

Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T-cell therapy expressing an affinity-enhanced T-cell recep- tor (TCR) to improve recognition of cancer cells expressing NY-ESO-1 and/or LAGE-1a. This master protocol will evaluate the safety and efficacy of next generation NY-ESO-1 specific TCR-T cells in SS/MRCLS or NSCLC.

Background: Letetresgene autoleucel (lete-cel; GSK3377794) is an autologous T cell therapy expressing an affinity-enhanced T cell receptors (TCR) to improve recognition of cancer cells expressing NY-ESO-1 and/or LAGE-1a. This study is recruiting. This substudy will evaluate the safety and efficacy of GSK3901961 in NSCLC.

P2, N=103, Active, not recruiting, GlaxoSmithKline | Recruiting --> Active, not recruiting

This outcome was correlated with enhanced expressions of IFN-γ and TNF-α, and an increased proportion of central memory T cells (CD45ROCD62L and CD45ROCCR7). Taken together, these data provide preclinical evidence for the combined use of DAC and NY-ESO-1-specific dTCR-T cells for the treatment of AML.

SS and MRCLS eligible patients received different dose lymphodepleting regimens (LDR) of fludarabine and cyclophosphamide depending on trial and cohort (table 1).3,4 For the present NY-ESO-1 expression analysis, the distribution of the NY-ESO-1 TP-score is displayed as boxplots allowing simultaneous visual comparisons of the range of expression across response, indication, and LDR. Observed range of response may be supportive of a cut-off in SS of less than 50% TP-score given that three patient responders had low to moderate (<50% TP-score) NY-ESO-1 expression, and that MRCLS cut-off was set at ≥30%. Further exploration of TP-score is underway in a current phase II trial of NY-ESO-1 TCR T-cell therapy (NCT03967223).

We induced NY-ESO-1 expression in vitro in human GBM cell lines (U251) and patient-derived gliomaspheres using the demethylating agent decitabine (DAC)... These results reveal a feasible strategy of cancer testis antigen promoter demethylation which creates an inducible tumor antigen for immunotherapeutic targeting. We speculate that DAC induced upregulation of NY-ESO-1 and co-expressed cancer testis antigens renders tumor recognition by NY-ESO-1 specific T cells.