P1, N=44, Recruiting, M.D. Anderson Cancer Center | Suspended --> Recruiting

P1, N=12, Terminated, GlaxoSmithKline | Trial completion date: Dec 2025 --> Jun 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2025 --> Jun 2023; The study was terminated due to a change in GSK's R&D priorities.

We also found that the in vitro activity of IgG-T-TCE-NY could be leveraged by various anti-CD3 antibodies and Fc silencing. The IgG-T-TCE-NY efficiently inhibited tumor growth in a tumor-PBMC co-engrafted mouse model without any obvious toxicities.

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, N=15, Recruiting, Radboud University Medical Center | Trial completion date: Jul 2024 --> Jul 2025 | Trial primary completion date: Dec 2023 --> Dec 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

P1, N=44, Suspended, M.D. Anderson Cancer Center | Not yet recruiting --> Suspended

The combination of NY-ESO-1 and p53 antibody responses to CEA and CA19-9 increases the diagnostic accuracy of gastric cancer. Serum NY-ESO-1 and p53 antibodies may be useful tumor markers for gastric cancer.

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.

P1/2, N=34, Terminated, GlaxoSmithKline | Phase classification: P1b/2a --> P1/2

P1, N=20, Not yet recruiting, University of Southern California | Trial completion date: Nov 2026 --> Apr 2027 | Initiation date: Nov 2023 --> Apr 2024 | Trial primary completion date: Nov 2025 --> Apr 2026

Our findings suggest that dual-targeted immunotherapy may have a superior antitumor effect. Our study presents a technique to evolve novel, robust, timely therapeutic strategies and interventions for EC and other malignancies.

Serum NY-ESO-1 antibodies may be a useful predictive marker for postoperative recurrence in gastric cancer.

C-MET and NY-ESO1 do not have any clinical correlations. EGFR can potentially serve as target in future clinical immune therapy trials.

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

P1/2, N=44, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting | Initiation date: May 2024 --> Nov 2023

Furthermore, experimental results have also demonstrated the repeatability of the proposed biosensor. This proposed biosensor features label-free, compactness, and fast response, which could be potentially applied in the diagnosis of esophageal cancer.

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.

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.

P1, N=20, Not yet recruiting, University of Southern California | Trial completion date: Apr 2026 --> Nov 2026

Background: Patients with intermediate and higher-risk MDS are generally treated with the DNA hypomethylating agents (HMAs) azacytidine and decitabine...This open-label, non-randomized single center Phase 1 study used an HLA unrestricted NY-ESO-1 vaccine (CDX-1401 (1 mg) + poly-ICLC (1.8 mg)) in combination with standard dose decitabine (20mg/m2/d x 5 days) and nivolumab (3 mg/kg every 2 weeks), 4 cycles of combination therapy were planned on study; patients deriving clinical benefit could continue treatment at the discretion of the treating physician... These results suggest that the use of immunotherapy to induce effective, cytotoxic anti-tumor T cell responses depends upon the myeloid immunologic milieu in MDS patients. The critical importance of cDC1 function has recently been described and appreciated in the context of solid tumor immunotherapy. The observation of both numerical and functional defects of this cell population in patients with myeloid neoplasia provides a possible explanation for the disappointing efficacy of immunotherapies in this disease state.

Our findings underscore the specific targeting potential of engineered TCR T cells against NY-ESO-1-positive tumors. Further comprehensive in vivo investigations are essential to thoroughly validate these results and effectively harness the intrinsic potential of genetically engineered T cells for combating cancer.

P1/2, N=73, Active, not recruiting, PDC*line Pharma SAS | Recruiting --> Active, not recruiting | Trial completion date: Sep 2025 --> Dec 2025 | Trial primary completion date: Sep 2025 --> Dec 2025

From cancer vaccines to engineered cellular therapy approaches, a multitude of immunotherapies targeting CTA's are coming to the forefront of oncology. Although the efficacy of such approaches have yet to provide convincing evidence of durable response, early phase clinical trial data has resulted in some exciting findings which will have significant potential to act as a platform for future practice changing technologies.

P1, N=44, Not yet recruiting, M.D. Anderson Cancer Center

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.

P2, N=184, Active, not recruiting, BioNTech SE | Recruiting --> Active, not recruiting

The current cancer vaccines targeting NY-ESO-1 have various types, including Dendritic cells (DC)-based vaccines, peptide vaccines, protein vaccines, viral vaccines, bacterial vaccines, therapeutic whole-tumor cell vaccines, DNA vaccines and mRNA vaccines, which exhibit their respective benefits and obstacles in the development and application. Here, we summarized the current advances in cancer vaccines targeting NY-ESO-1 for solid cancer treatment, aiming to provide perspectives for future research.

P1, N=7, Terminated, GlaxoSmithKline

P1/2, N=64, Recruiting, PDC*line Pharma SAS | Trial completion date: Aug 2024 --> Sep 2025 | Trial primary completion date: Aug 2024 --> Sep 2025

P1, N=20, Not yet recruiting, University of Southern California | Trial primary completion date: Mar 2025 --> Oct 2025

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.

P1, N=15, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed

A phase 1 trial demonstrating the safety and efficacy of a novel NY-ESO-1-specific TCR-T cells by Pan et al. is a major step forward for adoptive T cell therapy in the clinical practice of advanced soft tissue sarcomas.

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).

Key eligibility criteria were: age ≥10 years; HLA-A*02:01, A*02:05, or A*02:06; NY-ESO-1+ (≥30% of cells 2+/3+); optional bridging therapy consisting of 2 cycles of doxorubicin (dox) between apheresis and lymphodepletion (LD); and measurable disease. Pts received fludarabine (range: 60–120 mg/m^2) and cyclophosphamide (range: 1800–3600 mg/m^2) for LD, and a transduced T-cell dose between 1 to 15x10^9... This study highlights the challenge to enroll advanced/metastatic treatment-naïve rare sarcoma pts in a cell therapy trial, with 7 pts enrolled over ~2.5 years. Encouraging efficacy was seen in a small population of treatment-naïve pts in the advanced/metastatic setting with 80% ORR, with all responses ongoing at the time of this analysis. The TEAEs for SS1 are consistent with the known safety profile of lete-cel.

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

P1, N=20, Not yet recruiting, University of Southern California

Methods Two first-in-class, 3rd generation TCR-T therapies, MDG1015 and MDG2011, were developed using optimal affinity TCRs specific for a cancer-testis antigen, NY-ESO-1/LAGE-1a, and a neoantigen, mutated KRAS G12V, respectively. Conclusions The combination of optimal affinity TCRs combined with the PD1-41BB CSP provides strong protection of TCR-T cells against two variable mechanisms of TME immunosuppression based on the demonstration of CSP-enhanced poly-cytokine secretion, proliferation and mitigation against exhaustion in vitro. This observation warrants application in the clinic for this novel approach to potentially overcome the major challenges in solid tumor TMEs.