P1/2, N=54, Not yet recruiting, M.D. Anderson Cancer Center

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

P=N/A, N=6, Not yet recruiting, China Immunotech (Beijing) Biotechnology Co., Ltd.

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

P1/2, N=21, Not yet recruiting, Estrella Biopharma, Inc.

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.

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

P2, N=0, Withdrawn, National Cancer Institute (NCI) | N=210 --> 0 | Trial completion date: Dec 2029 --> Mar 2024 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2028 --> Mar 2024

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

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

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

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.

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

P1/2, N=100, Recruiting, Affini-T Therapeutics, Inc. | Not yet recruiting --> Recruiting

P1, N=32, Recruiting, HRYZ Biotech Co. | Not yet recruiting --> Recruiting

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

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

P1, N=7, Completed, Immatics US, Inc. | Active, not recruiting --> Completed | N=22 --> 7 | Trial completion date: Dec 2024 --> Sep 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

Of 214 screened patients, 14 were treated (6, IMA101; 8, IMA101 and atezolizumab). Target-specific T cells expanded to constitute up to 78.7% of CD8+ cells. In conclusion, IMA101 was feasible and well tolerated, leveraging the potential of multi-targeted ACT that warrants further investigation.

P1, N=42, Recruiting, Christian Hinrichs | Trial primary completion date: Sep 2023 --> Sep 2025

P1, N=50, Recruiting, Immatics Biotechnologies GmbH | Phase classification: P1a/1b --> P1

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=106, Recruiting, Sanofi | Trial completion date: May 2030 --> Dec 2030 | Trial primary completion date: May 2030 --> Dec 2030

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.

One approach to overcome this hurdle is dual targeting by an antibody-T cell receptor (AbTCR) and a chimeric costimulatory signaling receptor (CSR) to two different antigens, in which both antigens are found together on the cancer cells, but not together on normal cells...By use of a AbTCR receptor comprising a newly developed TCR mimic monoclonal antibody (mAb) against the WT1 RMFPNAPYL (RMF) epitope/HLA-A2 complex, ESK2, and a secondary CSR comprising a scFv directed to CD33 linked to a truncated CD28 costimulatory fragment, this unique platform confers specific T cell cytotoxicity to the AML cells, while sparing healthy hematopoietic cells, including CD33+ myelomonocytic normal cells. These data suggest that this new platform, named AbTCR-CSR, through the combination of a AbTCR CAR and CSR could be an effective strategy to reduce toxicity and improve specificity and clinical outcomes in adoptive T cell therapy in AML.

P1, N=12, Recruiting, Cancer Institute and Hospital, Chinese Academy of Medical Sciences

P1, N=10, Recruiting, Lion TCR Pte. Ltd. | Trial completion date: Jul 2024 --> Jul 2028 | Trial primary completion date: Jul 2023 --> Jul 2026

All subjects received a single dose of 5x10e7 or 1x10e8 cells/kg of SCG101 TCR-T cells intravenously after lymphodepletion with cyclophosphamidefludarabine. SCG101, as a single agent, demonstrated significant antiviral and antitumor activity in subjects with HBV-related HCC. The persistence of TCR T cells, reduction of serum HBsAg, and tumor response proved on-target activity of SCG101. A phase I/II clinical trial to systematically evaluate the safety and efficacy of SCG101 has been initiated.

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

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.

P1, N=100, Recruiting, TScan Therapeutics, Inc. | Not yet recruiting --> Recruiting

P1/2, N=100, Not yet recruiting, Affini-T Therapeutics, Inc.

P1/2, N=16, Recruiting, Fred Hutchinson Cancer Center | Trial completion date: Dec 2025 --> Apr 2025 | Trial primary completion date: Dec 2025 --> Apr 2024

P1, N=17, Recruiting, HRYZ Biotech Co. | Not yet recruiting --> Recruiting

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.

P1/2, N=144, Active, not recruiting, Immunocore Ltd | Recruiting --> Active, not recruiting | Trial completion date: Jul 2025 --> Feb 2024 | Trial primary completion date: Jul 2025 --> Sep 2023

Importantly, HLA-A/B/C alleles were almost always lost together, indicating that HLA loss most frequently occurs through haplotype loss, informing a strategy to direct multiplexed TCR-T to the remaining HLA haplotype. Conclusions Overall, these data highlight the importance of a multiplexed TCR-T cell therapy targeting various intact tumor antigens presented on intact HLA alleles in order to effectively address solid tumors.

The persistence of TCR+ T cells, reduction of serum HBsAg, and tumor response are strongly correlated with the mechanism of action of SCG101. A phase I/II clinical trial to further evaluate the safety and efficacy of SCG101 is ongoing.