gavocabtagene autoleucel (TC-210)

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.

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.

P1/2, N=70, Recruiting, TCR2 Therapeutics | Trial primary completion date: Jun 2021 --> Dec 2021

TC-210 expansion and serum cytokine levels were serially measured. Seven patients (6 MPM, 1 ovarian) received a single gavo-cel intravenous infusion at the initial dose of 5x107/m2 either alone (dose level [DL] 0, n=1) or following lymphodepletion (LD) (DL1, n=6) with fludarabine (30mg/m2/day x4) and cyclophosphamide (600mg/m2/day x3)...Four patients had received ≥4 lines of therapy, including immune checkpoint inhibitors (n=5), the anti-mesothelin ADC anetumab ravtansine (n=1), and anti-mesothelin mRNA CAR-T (n=1)...CRS and pneumonitis events resolved with tocilizumab and corticosteroids... Intravenous systemic administration of gavo-cel was generally safe and resulted in three of seven patients having objective partial response. Dose escalation is ongoing at 1x108/m2. Updated clinical and translational data will be presented.