mipetresgene autoleucel (TBI-1301) / Takara - LARVOL DELTA

Study of TBI-1301 (NY-ESO-1 Specific TCR Gene Transduced Autologous T Lymphocytes) in Patients With Solid Tumors (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: University Health Network, Toronto | Trial completion date: Sep 2025 ➔ Nov 2026 | Trial primary completion date: Sep 2025 ➔ Nov 2026

Trial completion date • Trial primary completion date • Bladder Cancer • Esophageal Cancer • Genito-urinary Cancer • Liver Cancer • Lung Cancer • Melanoma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B • HLA-A

Multi-center Study of TBI-1301 (INN: Mipetresgene Autoleucel; Mip-cel) in Patients With NY-ESO-1 Positive Synovial Sarcoma (clinicaltrials.gov) - P3 | N=5 | Not yet recruiting | Sponsor: Takara Bio Inc.

New P3 trial • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

Early differentiation and memory transcription programs drive long-term persistence of NY-ESO-1 specific TCR-T cells in adoptive cell therapy (SITC 2024) - P1 | "Patients received an infusion of 5x109 cells on day 0 after lymphodepletion with cyclophosphamide (CY) alone (750 mg/m2 on day -7 and -6) or in combination with fludarabine (FLU) (30 mg/m2 on day -7 and -6)...Conclusions These data demonstrate sustained persistence of infused TBI-1301 T cells. Understanding the cell states of persisting TCR-T cells provides valuable insights for developing combination approaches to enhance the efficacy of new therapeutics. Ethics Approval Subjects underwent informed consent to a University Health Network Research Ethics Board protocol, UHN REB # 15-9534."

IO biomarker • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CCR7 • CD8 • CTAG1B • HLA-A • TCF7

Early differentiation and memory transcription programs drive long-term persistence of NY-ESO-1 specific TCR-T cells in adoptive cell therapy (SITC 2024) - P1 | "Patients received an infusion of 5x109 cells on day 0 after lymphodepletion with cyclophosphamide (CY) alone (750 mg/m2 on day -7 and -6) or in combination with fludarabine (FLU) (30 mg/m2 on day -7 and -6)...Conclusions These data demonstrate sustained persistence of infused TBI-1301 T cells. Understanding the cell states of persisting TCR-T cells provides valuable insights for developing combination approaches to enhance the efficacy of new therapeutics. Ethics Approval Subjects underwent informed consent to a University Health Network Research Ethics Board protocol, UHN REB # 15-9534."

IO biomarker • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CCR7 • CD8 • CTAG1B • HLA-A • TCF7

Study of TBI-1301 (NY-ESO-1 Specific TCR Gene Transduced Autologous T Lymphocytes) in Patients With Solid Tumors (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: University Health Network, Toronto | Trial completion date: Sep 2024 ➔ Sep 2025 | Trial primary completion date: Sep 2024 ➔ Sep 2025

Trial completion date • Trial primary completion date • Bladder Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatology • Liver Cancer • Lung Cancer • Melanoma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B • HLA-A

Treatment options for advanced or recurrent #SynovialSarcoma are limited. Kawai et al report on their work using #AdoptiveImmunotherapy with TBI-1301 to selectively target NY-ESO-1 54 positive tumor cells and find it a promising strategy. https://bit.ly/3GNfbHL

Study of TBI-1301 (NY-ESO-1 Specific TCR Gene Transduced Autologous T Lymphocytes) in Patients With Solid Tumors (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: University Health Network, Toronto | Trial completion date: Sep 2023 ➔ Sep 2024 | Trial primary completion date: Sep 2023 ➔ Sep 2024

Trial completion date • Trial primary completion date • Bladder Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatology • Liver Cancer • Lung Cancer • Melanoma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B • HLA-A

Study of TBI-1301 (NY-ESO-1 T Cell Receptor Gene Transduced Autologous T Lymphocytes) in Patients With Synovial Sarcoma (clinicaltrials.gov) - P1/2 | N=8 | Completed | Sponsor: Takara Bio Inc. | Active, not recruiting ➔ Completed

Trial completion • Gene Therapies • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B • HLA-A

TBI-1301 Immunotherapy Shows Improvement in Synovial Sarcoma Treatment (Targeted Oncology) - P1/2 | N=8 | NCT03250325 | Sponsor: Takara Bio Inc.| "Eight patients were treated in the phase 1/2 trial...and the overall response rate (ORR) was 50% (95% CI, 15.7-84.3)....For safety, all patients experienced AEs, and 7 of 8 patients (87.5%) had adverse drug reactions. No deaths were attributed to AEs. Cytokine release syndrome occurred in 4 of 8 patients (50%), but all patients recovered with treatment."

Cytokine release syndrome • P1/2 data • Oncology • Sarcoma • Synovial Sarcoma

Safety and Efficacy of NY-ESO-1 Antigen-specific T-cell Receptor Gene-Transduced T Lymphocytes in Patients with Synovial Sarcoma: A Phase I/II Clinical Trial. (PubMed, Clin Cancer Res) - "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."

IO biomarker • Journal • P1/2 data • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B • HLA-A

Results from phase I/II study of NY-ESO-1-specific TCR gene-transduced T cell therapy (TBI-1301, mipetresgene autoleucel) in patients with advanced synovial sarcoma. (ASCO 2023) - P1/2 | "TBI-1301 was infused at split dose of 5 x 109 cells following cyclophosphamide treatment at 750 mg/m2 for two days to HLA-A*02:01 or HLA-A*02:06 positive subjects with synovial sarcoma expressing NY-ESO-1, which were surgically unresectable and refractory to anthracycline therapy...All subjects who developed CRS recovered with prespecified treatment, in which 2 subjects were treated with symptomatic therapy, 1 subject was treated with tocilizumab and 1 subject was treated with both tocilizumab and corticosteroid... Adoptive immunotherapy with TBI-1301 to selectively target NY-ESO-1 positive tumors will become a promising treatment for advanced or recurrent synovial sarcoma with acceptable toxicity. Clinical trial information: NCT03250325."

Clinical • Metastases • P1/2 data • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B • HLA-A

Study of TBI-1301 (NY-ESO-1 Specific TCR Gene Transduced Autologous T Lymphocytes) in Patients with Solid Tumors (ESMO 2018) - P1; "A pre-conditioning lymphodepletion regimen of cyclophosphamide 750 mg/m2 will be used on Day -3 and Day -2 prior to infusion of cell product. The objectives of this study include assessing the safety profile of TBI-1301, determining the RP2D dose, and evaluating the efficacy of TBI-1301 via RECIST v1.1."

Clinical • IO biomarker • Melanoma • Ovarian Cancer • Sarcoma

Study of TBI-1301 (NY-ESO-1 Specific TCR Gene Transduced Autologous T Lymphocytes) in Patients With Solid Tumors (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: University Health Network, Toronto | Trial completion date: Sep 2022 ➔ Sep 2023 | Trial primary completion date: Sep 2022 ➔ Sep 2023 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • Bladder Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatology • Liver Cancer • Lung Cancer • Melanoma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Synovial Sarcoma • Urothelial Cancer • CTAG1B • HLA-A

NY-ESO-1 and XAGE-1B correlate with the formation of tertiary lymphoid structures and prognosis of cutaneous angiosarcoma (JSID 2022) - No abstract available.

NY-ESO-1 and XAGE-1B correlate with the formation of tertiary lymphoid structures and prognosis of cutaneous angiosarcoma (JSID 2022) - No abstract available.

NY-ESO-1 and XAGE-1B correlate with the formation of tertiary lymphoid structures and prognosis of cutaneous angiosarcoma (JSID 2022) - No abstract available.

NY-ESO-1 and XAGE-1B correlate with the formation of tertiary lymphoid structures and prognosis of cutaneous angiosarcoma (JSID 2022) - No abstract available.

Adoptive T cell therapy with TBI-1301 results in gene-engineered T cell persistence and anti-tumour responses in patients with NY-ESO-1 expressing solid tumours (ESMO 2019) - P1; " Patients underwent modest lymphodepletion with cyclophosphamide (750 mg/m2 on day -3 and -2) followed by a planned infusion of 5x10^9 manufactured TBI-1301 cells on day 0...CRS grade 1-2 was experienced by 5 patients, with two patients requiring tocilizumab... ACT with TBI-1301 cells is safe and clinically active. Results provided here confirm long-term persistence of gene-engineered T cells with higher frequencies of CD45RA+ CCR7+ CD8+ T cells in responding patients. Detailed biomarker analysis of persisting TBI-1301 cells will be presented."

Clinical • IO biomarker • PD(L)-1 Biomarker • Endometrial Cancer • Gynecologic Cancers • Melanoma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor

Termination of co-development and marketing agreement with Otsuka Pharmaceutical Takara Bio for gene therapy drug TBI-1301 [Google Translation] (Mix Online) - "Otsuka Pharmaceutical Co., Ltd. announced on November 10 that it has agreed to terminate the joint development and marketing agreement for 'NY-ESO-1 siTCR gene therapy drug' (development code: TBI-1301) created by Takara Bio....With the termination of the contract, the technology, intellectual property and other rights related to the product granted to Otsuka Pharmaceutical by Takara Bio will be returned to Takara Bio."

Licensing / partnership • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma

The addition of fludarabine to cyclophosphamide for lymphodepleting chemotherapy enhances the persistence of infused NY-ESO-1 TCR anticancer therapy TBI-1301. (ASCO 2022) - P1 | "Repeat infusions of TBI-1301 following lymphodepletion appears to be safe and to possess anti-tumor activity. Addition of FLU to the lymphodepletion regimen may contribute to longer persistence of gene-engineered T cells."

IO biomarker • Gene Therapies • Inflammation • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • CTAG1B • HLA-A

NY-ESO-1-specific redirected T cells with endogenous TCR knockdown mediate tumor response and cytokine release syndrome. (PubMed, J Immunother Cancer) - P1 | "The trial showed that endogenous TCR-silenced and affinity-enhanced NY-ESO-1 TCR-T cells were safely administered except for grade 3 lung injury. The TCR-T cell infusion exhibited significant tumor response and early-onset CRS in patients with tumors that express NY-ESO-1 at high levels. The differentiation properties of the manufactured T cells may be prognostic for TCR-T-related CRS."

Cytokine release syndrome • IO biomarker • Journal • Inflammation • Oncology • Respiratory Diseases • Solid Tumor • CCL2 • CD8 • CTAG1B • ENTPD1 • IL6

Study of TBI-1301 (NY-ESO-1 Specific TCR Gene Transduced Autologous T Lymphocytes) in Patients With Solid Tumors (clinicaltrials.gov) - P1 | N=22 | Recruiting | Sponsor: University Health Network, Toronto | Trial completion date: Sep 2021 ➔ Sep 2022 | Trial primary completion date: Sep 2021 ➔ Sep 2022

Trial completion date • Trial primary completion date • Bladder Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatology • Liver Cancer • Lung Cancer • Melanoma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Synovial Sarcoma • Urothelial Cancer • CTAG1B • HLA-A

Effect of minimal lymphodepletion prior to ACT with TBI-1301, NY-ESO-1 specific gene-engineered TCR-T cells, on clinical responses and CRS. (ASCO 2019) - P1; "...While the optimal LD regimen is not yet defined, most include both cyclophosphamide (CY) and fludarabine (FLU)...CRS resolved spontaneously in all but one patient who required tocilizumab due to grade 2 nausea/vomiting... TBI-1301 appears to be safe and to possess anti-tumor activity. Despite LD with CY alone, grade 1-2 CRS is induced. Additional cohorts to this study will examine the role of repeat infusions to enhance anti-tumor activity."

Clinical • IO biomarker • Melanoma • Oncology • Sarcoma

TBI-1301: Regulatory submission in Japan for synovial sarcoma in FY2021 (Otsuka) - Q1 FY2021 Results

Japanese regulatory • Sarcoma

Study of TBI-1301 (NY-ESO-1 Specific TCR Gene Transduced Autologous T Lymphocytes) in Patients With Solid Tumors (clinicaltrials.gov) - P1; N=22; Recruiting; Sponsor: University Health Network, Toronto; Trial completion date: Jan 2021 ➔ Sep 2021; Trial primary completion date: Jan 2021 ➔ Sep 2021

Clinical • Trial completion date • Trial primary completion date • Bladder Cancer • Esophageal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hepatology • Liver Cancer • Lung Cancer • Melanoma • Oncology • Ovarian Cancer • Sarcoma • Solid Tumor • Urothelial Cancer • CTAG1B