HLA-A*02

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.

P1/2, N=40, Suspended, Fred Hutchinson Cancer Center | Recruiting --> Suspended

To conclude, we suspect that the discrepancies between NGS and RT-PCR results were caused by the presence of a significant amount of circulating lymphoma cells in the peripheral blood sample. Lymphomagenic mutations may involve the histocompatibility antigen coding region and affect HLA expressed on malignant cells. This finding may be relevant for the selection of test material in primary and confirmatory HLA testing in patients with active hematological malignancies because of the strong impact of incorrect HLA typing on the procedure of a donor selection.

P1, N=29, Completed, University of Pennsylvania | Active, not recruiting --> Completed | Trial completion date: Sep 2024 --> Feb 2024 | Trial primary completion date: Sep 2024 --> Feb 2024

In patients with incurable HPV16+ solid tumors treated with SQZ-PBMC-HPV, an increase in CD8+ T cell density within the tumor parenchyma was associated with superior disease control rate and overall survival. The product composition for patients with increased CD8+ T cell density was enriched for T cells.

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.

However, a single-signaling domain chimeric antigen receptor (ssdCAR) targeting L1CAM, a cell adhesion protein frequently overexpressed in HPV16-induced cancer, prompted a synergistic effect that significantly enhanced the cytotoxic capacity of NK-92/CD3/CD8 cells armored with both TCR and ssdCAR when both receptors simultaneously engaged their respective targets, as shown by live microscopy of 2-D and 3-D co-cultures. Thus, virus-specific TCRs from the CD8+ T cell repertoire of healthy donors can be combined with a suitable ssdCAR to enhance the cytotoxic capacity of the effector cells and, indirectly, their specificity.

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

Clinical Trial Registration Number: NCT04981119

P2, N=3, Terminated, Adaptimmune | N=45 --> 3 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2023 --> Apr 2023; Study was terminated due to difficulty recruiting subjects and lack of efficacy

P1/2, N=47, Terminated, Sumitomo Pharma America, Inc. | Phase classification: P1b/2 --> P1/2 | Completed --> Terminated; Sponsor's decision to terminate development of the program.

P4, N=250, Recruiting, Emory University | Trial completion date: Jun 2024 --> Dec 2025 | Trial primary completion date: Jun 2024 --> Dec 2025

P1/2, N=727, Recruiting, Immunocore Ltd | N=170 --> 727 | Trial completion date: Feb 2026 --> Jun 2026 | Trial primary completion date: Feb 2024 --> Jun 2026

Afami-cel treatment resulted in durable responses in heavily pre-treated patients with HLA-A*02 and MAGE-A4-expressing synovial sarcoma. This study shows that T-cell receptor therapy can be used to effectively target solid tumours and provides rationale to expand this approach to other solid malignancies.

The evolving landscape includes promising systemic treatments, such as tebentafusp, a novel immune-modulating bispecific fusion protein, and targeted therapies...Although recent progress has improved outcomes, ongoing research aims to address the unique challenges of UM and develop effective therapies, particularly for HLA-A*02:01-negative patients who represent a significant unmet medical need. This review comprehensively discusses the molecular characteristics of UM, risk stratification methods, and the current and future spectrum of regional and systemic therapeutic modalities.

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

P1/2, N=7, Active, not recruiting, Fred Hutchinson Cancer Center | Recruiting --> Active, not recruiting | N=16 --> 7 | Trial completion date: Apr 2025 --> Jan 2025 | Trial primary completion date: Apr 2024 --> Jan 2024

Several predicted microbiota-derived MoAs are recognized by T cells in HS and CP. Reactivity against TAAs was observed also in HS, primed by the homologous bacterial antigens. CD8+ T cells cross-reacting with MAGE-A1 and paired microbiota epitopes were identified in three subjects. Therefore, the microbiota can elicit an extensive repertoire of natural memory T cells to TAAs, possibly able to control tumor growth ("natural anti-cancer vaccination"). In addition, non-self MoAs can be included in preventive/therapeutic off-the-shelf cancer vaccines with more potent anti-tumor efficacy than those based on TAAs.

P1, N=180, Recruiting, Immunocore Ltd | N=108 --> 180

MSK-IMPACT successfully determined class I HLA genotypes in a large, multi-ethnic population of patients. A substantial proportion of patients were identified as potential candidates for HLA-matched trials, supporting local trial enrollment.

This represents a significant improvement over the conventional MM/GBSA method, which yields a Pearson correlation coefficient of 0.22. The computational protocol developed in this study can be applied to the computational screening of antigens for the MHC1 as well as other protein-peptide binding systems.

P1, N=5, Terminated, SQZ Biotechnologies | N=72 --> 5 | Trial completion date: Apr 2024 --> Nov 2023 | Active, not recruiting --> Terminated | Trial primary completion date: Apr 2024 --> Nov 2023; Corporate Decision

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

P1/2, N=50, Completed, Sabine Mueller, MD, PhD | Active, not recruiting --> Completed | Trial completion date: Nov 2024 --> Dec 2023 | Trial primary completion date: Nov 2024 --> Dec 2023

P3, N=680, Recruiting, Immunocore Ltd | Not yet recruiting --> Recruiting

P1/2, N=20, Recruiting, Adaptimmune | Not yet recruiting --> Recruiting

P1, N=120, Recruiting, Adaptimmune | Trial primary completion date: Sep 2023 --> Dec 2025

P1/2, N=23, Terminated, T-knife GmbH | N=48 --> 23 | Trial completion date: Jun 2037 --> Jan 2024 | Suspended --> Terminated | Trial primary completion date: Jun 2024 --> Jan 2024; Sponsor decision.

P1/2, N=75, Terminated, Immunocore Ltd | N=144 --> 75 | Trial completion date: Feb 2024 --> Sep 2023 | Active, not recruiting --> Terminated; The Sponsor terminated the study and there is no further enrollment. Endpoints will not be assessed for this trial.

This is so far the largest study to comprehensively evaluate neoantigen prediction models using experimentally validated neopeptides. Our results demonstrate the reliability and effectiveness of ImmuneMirror for neoantigen prediction.

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.

P1/2, N=230, Recruiting, A2 Biotherapeutics Inc. | Not yet recruiting --> Recruiting

P1/2, N=113, Completed, Immunocore Ltd | Phase classification: P1b/2 --> P1/2

P1, N=71, Active, not recruiting, Adaptimmune | N=52 --> 71 | Trial completion date: Sep 2035 --> Sep 2032

Several predictive biomarkers have been proposed for ICI therapies but have not been incorporated into Australian clinical practice guidelines. Further research, validation, and assessment of clinical utility is required before more prognostic and predictive biomarkers are fluidly integrated into routine care.

Of note, a comprehensive analysis revealed that a broad range of amino acid sequences of the MAGE-A4p peptide were critical for the recognition of MAGE-A4 pMHC by these CAR-T cells, and no cross-reactivity to analogous peptides was observed. Thus, MAGE-A4-targeted CAR-T therapy using this scFv antibody may be a promising and safe treatment for solid tumors.

P1/2, N=11, Completed, Dana-Farber Cancer Institute | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Feb 2023

P1, N=100, Recruiting, TScan Therapeutics, Inc. | Initiation date: Nov 2023 --> Feb 2024

P1, N=15, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Sep 2024 --> Jun 2025 | Trial primary completion date: Dec 2023 --> Jun 2024

P1/2, N=230, Not yet recruiting, A2 Biotherapeutics Inc.

P1/2, N=160, Recruiting, A2 Biotherapeutics Inc.