HLA-A*02:01

P2, N=66, Active, not recruiting, Adaptimmune | Recruiting --> Active, not recruiting

Extensive HLA-A*02 and antigen expression testing was performed to identify potential participants. Lete-cel was generally well tolerated and had no unexpected AEs. Anti-tumor activity was observed in a limited number of patients.

P1/2, N=26, Completed, Erasmus Medical Center | Recruiting --> Completed

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

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.

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

We showed that the developed DNA vaccine, applied using a novel intradermal application strategy, can be administered safely. Further research with improved vaccine formats is required to show possible clinical benefit of DNA vaccination.

P1, N=24, Suspended, Fred Hutchinson Cancer Center | Trial completion date: Jul 2025 --> Jul 2028 | Trial primary completion date: Oct 2024 --> Oct 2027

P2; Trial completion date: Nov 2028 --> Jun 2029 | Initiation date: Nov 2023 --> Jun 2024 | Trial primary completion date: Nov 2026 --> Jun 2026

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

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

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.

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

Taken together, we present novel neoantigens with promise as immunotherapy targets for AML and other hematologic malignancies with FLT3-D835 mutations. Future studies will evaluate the efficacy of Neo-D835H-specific TCR-engineered T-cell-based immunotherapy in vivo in patient-derived xenograft murine model and TCR-based therapeutic approaches targeting other FLT3-TKD mutations.

Targeting MiHAs HA-1 or HA-2 with TSC-100/ 101 following HCT shows early safety and biomarker evidence of efficacy by completing elimination of all detectable patient hematopoietic cells, normal or malignant, thereby reducing relapse risk. Updated results will be presented at the meeting.

P1b/2, N=113, Completed, Immunocore Ltd | Active, not recruiting --> Completed | N=312 --> 113 | Trial completion date: Nov 2023 --> Jun 2023

This 3-year analysis supported a continued long-term benefit of tebentafusp for overall survival among adult HLA-A*02:01-positive patients with previously untreated metastatic uveal melanoma. (Funded by Immunocore; IMCgp100-202 ClinicalTrials.gov number, NCT03070392; EudraCT number, 2015-003153-18.).

We found that CRP impaired immune response of CD8 T cells via FcγRIIb-p38MAPK-ROS signaling pathway. The study casted new insights into the role of CRP in anti-myeloma immunity, providing implications for future immunotherapy in MM.

Tebentafusp, a bispecific T-cell receptor fusion protein directed against gp100 and CD3, can improve survival in patients with metastatic uveal melanoma and was recently approved for the treatment of HLA-A*02:01-positive uveal melanoma patients. With adequate therapy, including the application of rasburicase, the patient made a full recovery. It is important to raise awareness of the adverse event profile of this new therapeutic approach among healthcare professionals to promptly recognize and treat side effects.

P2; N=44; Not yet recruiting; Sponsor:Diwakar Davar

P1/2, N=44, Not yet recruiting, M.D. Anderson Cancer Center

P1b/2, N=312, Active, not recruiting, Immunocore Ltd | Trial completion date: Jan 2025 --> Nov 2023 | Trial primary completion date: Jan 2025 --> Jul 2023 | Recruiting --> Active, not recruiting

In addition to the primary safety objectives, secondary objectives of efficacy (progression-free survival, overall survival) and patient-reported quality of life outcomes will be assessed. Trial sponsor: CureVac SE, Germany.

P1, N=7, Terminated, GlaxoSmithKline

P1/2, N=24, Recruiting, Erasmus Medical Center | Trial primary completion date: Jul 2023 --> Jul 2024

Tebentafusp is a relatively new licenced therapy option for HLA-A 02:01 positive advanced uveal melanoma. We conclude that gemcitabine and treosulfan treatment can delay tumour progression. Adjustments to the treatment dose are necessary in case of adverse events under therapy. Further investigations are needed to show which patients benefit from initial dose reduction in the treatment.

Our ongoing study highlights the potential of measles virotherapy to both mediate direct tumor cell lysis, as well as enhance anti-tumor immune response as oncolytic vaccine in multiple sarcoma sub-entities. Currently, we are refining MeV sensitivity signature by integrative transcriptomics and proteomics analysis that may act as a predictive biomarker for the response to measles virotherapy. In an in vitro setting, we demonstrate that an oncolytic MeV vaccine carrying NY-ESO-1 can enhance the T cell-mediated killing of sarcoma cells, thereby providing a successful proof-of-concept for the application of MeV-based oncolytic vaccine.

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

Conclusions ImmTAC-mediated redirection of T cells reprograms pro-tumoral M2 macrophages towards anti-tumoral M1 macrophages in vitro and in tebentafusp-treated mUM patients. These results demonstrate how tebentafusp re-shapes the tumor microenvironment to enhance the anti-tumor activity of T cells.

Conclusions HLA-A status predicted clinical outcomes of patients receiving ICB. HLA genotyping could be incorporated early into the diagnostic work-up of patients with solid cancers as a predictive and selective biomarker.

P1, N=73, Completed, H. Lee Moffitt Cancer Center and Research Institute | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Jan 2023

P1, N=12, Not yet recruiting, University of California, San Francisco | Trial completion date: Dec 2028 --> Aug 2029 | Initiation date: May 2023 --> Aug 2023 | Trial primary completion date: Dec 2028 --> Aug 2029

P1, N=5, Terminated, GlaxoSmithKline

P1, N=24, Recruiting, Neogene Therapeutics, Inc. | Not yet recruiting --> Recruiting

Patients received lymphodepletion (fludarabine, cyclophosphamide), followed by T-cell infusion and low-dose IL2 (Cohort 1). Patients in Cohort 2 received atezolizumab for up to 1 year (NCT02876510)...This study demonstrates the feasibility and tolerability of an actively personalized ACT directed to multiple defined pHLA cancer targets. Results warrant further evaluation of multi-target ACT approaches using potent high-avidity TCRs.

P2, N=66, Recruiting, Adaptimmune | Not yet recruiting --> Recruiting | Initiation date: Mar 2023 --> Jun 2023

No abstract available

P1/2, N=24, Recruiting, Erasmus Medical Center

At maximum target doses, the safety of tebentafusp with checkpoint inhibitors was consistent with safety of each individual therapy. Tebentafusp with durvalumab demonstrated promising efficacy in heavily pretreated patients with mCM, including those who progressed on prior anti-PD(L)1.

P1, N=24, Not yet recruiting, Neogene Therapeutics, Inc.

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.

The low current treatment efficacy for mUM, alongside a poor long-term prognosis and high mortality rates, gives precedence for the approval of tebentafusp to be groundbreaking in its clinical impact. This review will discuss the pharmacodynamic and pharmacokinetic profile, and the clinical trials used to evaluate the safety and efficacy of tebentafusp.