gavocabtagene autoleucel (TC-210)

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.

P1/2, N=57, Active, not recruiting, TCR2 Therapeutics | N=36 --> 57 | Trial primary completion date: Nov 2028 --> Nov 2024

P1/2, N=36, Active, not recruiting, TCR2 Therapeutics | Recruiting --> Active, not recruiting | N=175 --> 36 | Trial completion date: Apr 2026 --> Nov 2028 | Trial primary completion date: Jul 2024 --> Nov 2028

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.

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.

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.

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.

P1/2, N=175, Recruiting, TCR2 Therapeutics | N=70 --> 175 | Trial completion date: Jan 2023 --> Apr 2026 | Trial primary completion date: Dec 2021 --> Jul 2024

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.

The abstract for this presentation has not been submitted or is currently under embargo until August 18, 2021 at 16:00 MDT.