HLA-A*02

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.

P=N/A, N=200, Recruiting, A2 Biotherapeutics Inc.

P1/2, N=48, Suspended, T-knife GmbH | Recruiting --> Suspended

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

Detectable ctDNA at baseline did not correlate with progression. Early response to tebentafusp may be incompletely captured by conventional imaging, leading to a need to consider both tumor morphology and metabolism.

We have preclinically validated an iCAR NOT gate technology broadly applicable for targeting HER2 expression in the context of A2 LOH. This approach is designed to prevent off tumor toxicity while allowing highly potent antitumor activity.

P1, N=59, Completed, Hoffmann-La Roche | Recruiting --> Completed | N=220 --> 59 | Trial completion date: Feb 2026 --> Aug 2023 | Trial primary completion date: Feb 2026 --> Aug 2023

Trial 2: NCT05473910 (TSCAN-001, TScan Inc.) is a multi-arm non-randomized controlled Phase 1 study evaluating the safety and efficacy of TScan's TSC100 and TSC101 - allogeneic T-cell receptor-engineered T cells that target haematopoietically restricted antigens HA-1 and HA-2 respectively, both presented on HLA-A*02:01, in mismatched reduced-intensity conditioning (RIC)-haplo donor HCT recipients. Additionally, where MRD results were available, AH CD33 iMC was associated with MRD (p=0.019, N=79) (Table 3). These interim results suggest a potential utility of MC measured by AlloHeme, an ultra-sensitive NGS-based chimerism monitoring solution, as a non-invasive predictive biomarker for treatment response and relapse in post allo-HCT patients.

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

The prognostic value of complete donor chimerism by AlloHeme was evaluated in the ACROBAT study (NCT04635384) in which 73 patients achieved >99.9% chimerism in CD33+ cells and, after median follow-up of 9 months/ 270 days (range 72-608 days), 3 relapsed (4%), comparing favorably with 18-20% 6-month relapse rates in CIBMTR data. In summary, TSC-100 and TSC-101 post-HCT induce MRD negativity and complete donor chimerism which may be associated with substantially reduced relapse rates.

P1, N=15, Recruiting, University Hospital Tuebingen | Trial completion date: May 2024 --> Aug 2025 | Trial primary completion date: May 2023 --> Aug 2024

Tebentafusp was previously shown to provide an OS benefit compared to checkpoint inhibitors or chemotherapy in untreated mUM. Propensity score analysis demonstrated a similar OS benefit for tebentafusp compared with N+I. These data further support tebentafusp as the standard of care in previously untreated HLA-A*02:01+ adult patients with mUM.

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