gavocabtagene autoleucel (TC-210) / Adaptimmune - LARVOL DELTA

Characterization of CAR-T cellular kinetics and efficacy in solid tumor patients with and without prior lymphodepletion chemotherapy using a PBPK-PD model. (PubMed, J Pharmacokinet Pharmacodyn) - "Model was developed based on digitized individual level CK, categorical antitumor activity and percentage tumor antigen expression dataset from following phase-1 dose-escalation studies: (A) anti-mesothelin CAR-T in multiple cancer indications (n = 15, cohorts w/ and w/o LDC), (B) gavocabtagene autoleucel (n = 7, w/ and w/o LDC) in multiple indications, (C) anti-glypican 3 CAR-T in advanced hepatocellular carcinoma (n = 13, dose-range 0.7-5.18 billion) and (D) anti-PSMA/TGFβ CAR-T in prostate cancer (n = 10, w/ and w/o LDC)...Using model simulation, CAR-T cell expansion was found to be dependent on initial tumor burden and antigen positive tumor fraction. The developed PBPK-PD model could be leveraged as an effective tool in future to provide mechanistic understanding on CK-PD behavior of cell therapies targeting solid tumors."

IO biomarker • Journal • Genito-urinary Cancer • Hematological Disorders • Hematological Malignancies • Hepatocellular Cancer • Oncology • Prostate Cancer • Solid Tumor • GPC3 • TGFB1

Phase 1/2 Trial of Gavo-cel (TC-210) in Patients With Advanced Mesothelin-Expressing Cancer (clinicaltrials.gov) - P1/2 | N=57 | Active, not recruiting | Sponsor: TCR2 Therapeutics | N=36 ➔ 57 | Trial primary completion date: Nov 2028 ➔ Nov 2024

Enrollment change • IO biomarker • Trial primary completion date • Biliary Cancer • Cholangiocarcinoma • High Grade Serous Ovarian Cancer • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Pleural Mesothelioma • Solid Tumor • MSLN

Phase 1/2 Trial of Gavo-cel (TC-210) in Patients With Advanced Mesothelin-Expressing Cancer (clinicaltrials.gov) - P1/2 | N=36 | Active, not recruiting | Sponsor: TCR2 Therapeutics | Recruiting ➔ Active, not recruiting | N=175 ➔ 36 | Trial completion date: Apr 2026 ➔ Nov 2028 | Trial primary completion date: Jul 2024 ➔ Nov 2028

Enrollment change • Enrollment closed • IO biomarker • Metastases • Trial completion date • Trial primary completion date • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • MSLN

Functional enhancement of mesothelin-targeted TRuC-T cells by a PD1-CD28 chimeric switch receptor. (PubMed, Cancer Immunol Immunother) - "T cells expressing a mesothelin (MSLN)-specific T cell receptor fusion construct (TRuC), called TC-210, have demonstrated robust antitumor activity in preclinical models of mesothelioma, ovarian cancer, and lung cancer. These data demonstrate that integration of a PD1-CD28 CSR into TRuC-T cells improves effector function, resistance to exhaustion, and prolongs persistence. Based on these findings, TC-510 is currently being evaluated in patients with MSLN-expressing solid tumors."

IO biomarker • Journal • Lung Cancer • Mesothelioma • Oncology • Ovarian Cancer • Solid Tumor • CD28 • MSLN • PD-1

Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: phase 1/2 trial interim results (Nature) - P1/2 | N=175 | NCT03907852 | Sponsor: TCR2 Therapeutics | "Thirty-two patients received gavo-cel at increasing doses either as a single agent (n = 3) or after lymphodepletion (LD, n = 29). Dose-limiting toxicities of grade 3 pneumonitis and grade 5 bronchioalveolar hemorrhage were noted. The RP2D was determined as 1 × 108 cells per m2 after LD. Grade 3 or higher pneumonitis was seen in 16% of all patients and in none at the RP2D; grade 3 or higher cytokine release syndrome occurred in 25% of all patients...In 30 evaluable patients, the overall response rate and disease control rate were 20% (13% confirmed) and 77%, respectively, and the 6-month overall survival rate was 70%."

P1/2 data • Mesothelioma • Oncology • Solid Tumor

Mesothelin-targeting T cell receptor fusion construct cell therapy in refractory solid tumors: phase 1/2 trial interim results. (PubMed, Nat Med) - "In 30 evaluable patients, the overall response rate and disease control rate were 20% (13% confirmed) and 77%, respectively, and the 6-month overall survival rate was 70%. Gavo-cel warrants further study in patients with mesothelin-expressing cancers given its encouraging anti-tumor activity, but it may have a narrow therapeutic window."

Journal • P1/2 data • Hematological Disorders • Oncology • Pneumonia • Solid Tumor • MSLN

Phase 1 trial of gavocabtagene autoleucel (gavo-cel, TC-210) in patients (pts) with treatment refractory mesothelioma and other mesothelin-expressing solid tumors. (ASCO 2023) - P1/2 | "A single IV gavo-cel infusion at the RP2D was associated with a manageable toxicity profile and high rates of disease control, including objective responses in pts with refractory MPM and OvC. A phase 2 study is underway testing the safety and efficacy of gavo-cel in combination with checkpoint inhibitors in pts with mesothelin-expressing solid tumors. Clinical trial information: NCT03907852."

Clinical • IO biomarker • P1 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Hematological Disorders • Immune Modulation • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Pneumonia • Solid Tumor • CD8 • CXCL8 • IFNG • IL6 • MSLN • PD-L1 • PVR • TNFA

Profiling of tumor infiltrating T cells in malignant pleural/peritoneal mesothelioma (MPM) and ovarian cancer patients as part of a Phase 1 clinical trial of gavo-cel (TC-210) (AACR 2023) - P1/2 | "Dose level 3 (1x108 TRuC cells/m2 following lymphodepletion with cyclophosphamide and fludarabine) was selected as the Recommended Phase 2 Dose (RP2D) for the ongoing phase 2 portion of the trial. We are currently evaluating the tumor immune contexture in phase 2, focusing on differences across tumor types with regards to TIL content, T cell influx, and correlations with response. We will also explore additional markers such as PD-1 and TIGIT, to profile the exhaustion state of immune cells and their spatial relationship with infiltrating gavo-cel T cells."

Clinical • IO biomarker • P1 data • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Ovarian Cancer • Solid Tumor • CD8 • MSLN • PD-1 • PVR • TIGIT

TCR² Therapeutics Reports Fourth Quarter and Full-Year 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - P1/2 | N=175 | NCT03907852 | Sponsor: TCR2 Therapeutics | "gavo-cel: First readout from the ongoing Phase 2 portion of the gavo‑cel Phase 1/2 clinical trial in ovarian cancer in combination with checkpoint inhibitors and redosing strategies anticipated in the second half of 2023. Interim update, including key translational data, in patients with mesothelioma treated with gavo‑cel in combination with checkpoint inhibitors in the Phase 2 portion of the gavo-cel Phase 1/2 clinical trial before the focus was narrowed to ovarian cancer anticipated midyear 2023. Tumor regression has been observed in 93% of patients in the Phase 1 trial. The response rate was 29% in patients with ovarian cancer with a median progression free survival (PFS) of 5.8 months and a median overall survival (OS) of 8.1 months. The response rate in mesothelioma was 21% with a median PFS of 5.9 months and a median OS of 11.2 months."

P1/2 data • Gynecologic Cancers • Mesothelioma • Oncology • Ovarian Cancer • Solid Tumor

Mesothelin-targeting T cells bearing a novel T cell receptor fusion construct (TRuC) exhibit potent antitumor efficacy against solid tumors. (PubMed, Oncoimmunology) - "These data highlight TC-210 T cells as a promising cell therapy for treating MSLN-expressing cancers. The differentiated profile from CAR-T cells may translate into better efficacy and safety of TRuC-T cells for solid tumors."

Journal • Hematological Malignancies • Lung Cancer • Mesothelioma • Oncology • Ovarian Cancer • Solid Tumor • MSLN

The Functional Activity of Gavo-cel TRuC-T Cells is not Impaired by Soluble Mesothelin (SITC 2022) - P1/2 | "Furthermore, gavo-cel demonstrates potent efficacy in vivo in a tumor model characterized by circulating sMSLN. Conclusions Our data indicate that both gavo-cel and allogeneic MSLN-targeting TRuC-T cells are not susceptible to functional suppression by sMRPs, even at supraphysiological levels that far exceed those found in cancer patients."

Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor • MSLN

[VIRTUAL] Gavocabtagene autoleucel (gavo-cel, TC-210) dose escalation in refractory mesothelin-expressing solid tumors (ESMO 2021) - P1/2 | "One DLT (gr3 pneumonitis at DL1) and 2 gr3 CRS events were reported, both resolving with tocilizumab/corticosteroids. The toxicity profile of gavo-cel was manageable. Activity was observed among pts with refractory MSLN-expressing solid tumors. Dose escalation is ongoing to determine the RP2D."

IO biomarker • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Lung Cancer • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Refractory Ovarian Cancer • Solid Tumor • MSLN • TP53

TCR² Therapeutics: Refocused Pipeline Puts It On A Solid Path (SeekingAlpha) - P1/2 | N=175 | NCT03907852 | Sponsor: TCR2 Therapeutics | "The main clinical program to go over in the pipeline is the use of gavo-cel, which is being developed for the treatment of mesothelin-positive solid tumors...It was noted that tumor regression was observed in 28 out of the 30 (93%) of evaluable patients with a disease control rate (DCR) of 77% who took gavo-cel. It wasn't that bad with respect to the other endpoint measurements as well, such as those relating to progression-free survival [PFS] and overall survival [OS]. PFS was 5.6 months and then OS was 11.2 months, which is pretty good durability for this patient population. This is not bad clinical data either, especially since TCR² Therapeutics was forced to go down a few dose levels after many cohorts."

P1/2 data • Oncology • Solid Tumor

TCR² Therapeutics Announces Pipeline Priorities for 2023 (GlobeNewswire) - "gavo-cel Phase 2 clinical trial now focused on ovarian cancer cohort with first meaningful durability data expected in 2H 2023. Second-generation enhanced programs TC-510 and TC-520 prioritized with TC-510 Phase 1 clinical trial ongoing and first meaningful objective response data expected in 2H 2023. Company to be streamlined with approximately 40 percent reduction in workforce."

P1 data • P2 data • Gynecologic Cancers • Ovarian Cancer • Solid Tumor

TCR² Therapeutics Presents Preclinical Data on Functional Activity of Gavo-cel at the Society for Immunotherapy of Cancer (GlobeNewswire) - "TCR2 Therapeutics...announced the poster presentation of new preclinical data at the Society for Immunotherapy of Cancer (SITC) Conference 37th Annual Meeting, taking place November 8-12, 2022....Levels of sMSLN 50-fold higher than were measured in MPM patients had no observed impact on the functional activity of gavo-cel T cells with respect to tumor cell killing and cytokine production. These results suggest that the levels of sMSLN present in the circulation of MPM patients likely do not pose a concern for the clinical activity of gavo-cel."

Preclinical • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Oncology • Solid Tumor • Thoracic Cancer

gavo-cel Continues to Demonstrate Clinical Benefit in Solid Tumors with Additional RECIST Reponses in Ovarian Cancer and Mesothelioma (GlobeNewswire) - P1/2 | N=175 | NCT03907852 | Sponsor: TCR2 Therapeutics | "As of the September 9, 2022 data cutoff, 32 patients (including 23 mesothelioma, eight ovarian cancer and one cholangiocarcinoma) had received a single gavo-cel infusion in the Phase 1 portion of the clinical trial....gavo-cel demonstrated a disease control rate (DCR) of 77%, which is defined in the Phase 1 portion of the trial as a response or sustained stable disease for at least three months post infusion....The overall response rate (ORR) among patients who received gavo-cel following lymphodepletion chemotherapy was 22% by BICR and 26% by investigator assessment. By BICR, the ORR was 21% among patients with malignant pleural/peritoneal mesothelioma (MPM) and 29% among those with ovarian cancer. The median overall survival (OS) for patients with MPM was 11.2 months, whereas the median progression-free survival (PFS) for patients with MPM was 5.6 months."

P1 data • Biliary Tract Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Gynecologic Cancers • Mesothelioma • Oncology • Ovarian Cancer • Solid Tumor

TCR^² Therapeutics to Announce Complete Phase 1 Portion of the Gavo-cel Phase 1/2 Clinical Trial for Mesothelin-Expressing Solid Tumors (GlobeNewswire) - "TCR2 Therapeutics...announced that the Company plans to discuss the complete Phase 1 portion of the gavo-cel Phase 1/2 clinical trial for mesothelin-expressing solid tumors in a premarket press release and conference call to be held on Wednesday, September 28th, 2022 at 8:00am E.T."

P1 data • Mesothelioma • Oncology • Solid Tumor

Phase 1/2 Trial of Gavo-cel (TC-210) in Patients With Advanced Mesothelin-Expressing Cancer (clinicaltrials.gov) - P1/2 | N=175 | Recruiting | Sponsor: TCR2 Therapeutics | N=70 ➔ 175 | Trial completion date: Jan 2023 ➔ Apr 2026 | Trial primary completion date: Dec 2021 ➔ Jul 2024

Enrollment change • IO biomarker • Trial completion date • Trial primary completion date • Biliary Cancer • Gastrointestinal Cancer • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Ovarian Serous Adenocarcinoma • Solid Tumor • MSLN

Gavo-Cel: A TRuC-T Cell Therapy Targeting Treatment Refractory Mesothelin-Expressing Solid Tumors (PEGS 2022) - "This presentation will give an introduction to the TRuC T cell platform, and outline the advantages of TRuC T cells over CAR T cells in solid tumors. Details around the ongoing clinical trials with TRuC T cells will also be shared."

Oncology • Solid Tumor • MSLN

Engineering off-the-shelf anti mesothelin t-cell receptor fusion construct (TRuC™) t-cells (AACR 2022) - "In comparison with control autologous TRuC-T cells targeting mesothelin (TC-210), allogeneic TRuC-Ts demonstrate extended tumor clearance in NSG xenograft models due to their enhanced expansion and persistence. To reduce host rejection and further boost the persistence of the allogeneic TRuC-T cells, we eliminated MHC class I surface expression by B2M gene knockout and over-expressed membrane-bound IL15 tethered to its receptor alpha. In summary we have engineered persistence enhanced, allogeneic TRuC-T cells that maintain the signaling properties of the TCR complex with improved efficacy compared to donor-matched autologous TRuC-T cells."

IO biomarker • Oncology • B2M • IL15 • MSLN

Expression of a membrane-tethered IL-15/IL-15 receptor fusion protein enhances the persistence of MSLN-targeted TRuC-T cells (SITC 2021) - "Finally, IL-15fu-enhanced TRuC-T cells could be observed in the blood long after the tumors were cleared. Conclusions These pre-clinical studies suggest that the IL-15fu can synergize with TC-210 to increase the potency and durability of response in patients with MSLN+ tumors."

IO biomarker • Hematological Malignancies • Lung Cancer • Mesothelioma • Oncology • Ovarian Cancer • Solid Tumor • CD8 • IL15 • MSLN

David S Hong, ESMO 2021: Gavocabtagene Autoleucel Dose Escalation in Refractory Mesothelin-expressing Solid Tumors (PART TWO) (Touch Oncology) - "TouchONCOLOGY joins Professor David S Hong...at ESMO 2021 to discuss the safety and activity of gavocabtagene autoleucel in a dose-escalation study in patients with refractory ovarian cancer, malignant mesothelioma, cholangiocarcinoma or non-small cell lung cancer."

Video

TCR² Therapeutics Reports Fourth Quarter 2021 Financial Results and Provides Corporate Update (GlobeNewswire) - "Anticipated Milestones - Gavo-cel: (i) Present the expanded and complete Phase 1 dataset for gavo-cel in the second quarter of 2022; (ii) Initiate the Phase 2 expansion cohort of the ongoing gavo-cel Phase 1/2 clinical trial in the first half of 2022; (iii) Provide an initial update from at least one of the Phase 2 expansion cohorts of the ongoing gavo-cel Phase 1/2 clinical trial in the second half of 2022."

P1 data • P1/2 data • Trial status • Oncology • Solid Tumor

TCR² Therapeutics Announces 2022 Strategic Priorities and Anticipated Milestones (GlobeNewswire) - "2022 Strategic Priorities and Anticipated Milestones: Gavo-cel: Update on Phase 2 expansion cohort initiation anticipated in 1H 2022, which is subject to Food and Drug Administration (FDA) feedback on the clinical trial design, Expanded and complete Phase 1 dataset on safety, efficacy and translational data anticipated in 1H 2022, Initial data from Phase 2 expansion cohort including safety, efficacy and translational data anticipated in 2H 2022."

Enrollment status • P1 data • P2 data • Cholangiocarcinoma • Gynecologic Cancers • Lung Cancer • Malignant Pleural Mesothelioma • Mesothelioma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer

TCR² Therapeutics and Arbor Biotechnologies Establish Collaboration to Advance Allogeneic TRuC-T Cell Therapies (GlobeNewswire) - "TCR2 Therapeutics Inc...and Arbor Biotechnologies...today announced that the two companies have entered into a strategic research collaboration and non-exclusive license agreement focused on the further development of a defined set of allogeneic TRuC-T cell therapies. The collaboration leverages Arbor’s proprietary CRISPR gene-editing technology, which is tailored to address the underlying pathology of genetic diseases, and TCR2’s’ first-in-class TRuC platform, which has demonstrated clinical activity in multiple treatment-refractory mesothelin-expressing solid tumor indications with its lead autologous program gavo-cel."

Licensing / partnership • Oncology • Solid Tumor