The first data are in for TCR2 Therapeutics’ lead program, and they look good. The T-cell therapy shrank tumors in five patients with mesothelin-expressing cancers, with two patients seeing enough shrinkage to be considered partial responders.
The data come from the first five patients in the phase 1 part of a phase 1/2 study. Although this portion of the study was geared to gauge safety and arrive at a dose for the phase 2 part, the company is “encouraged” by the results. It’s developing the treatment, dubbed TC-210, for patients whose cancers express mesothelin, a protein that TCR2 CEO Garry Menzel calls an “ideal” cancer target. Mesothelin is expressed in high levels in several cancers and in low levels in healthy tissue.
Of the five patients, one had ovarian cancer and four had mesothelioma, a cancer of the mesothelium—the thin tissue that lines the lung, chest wall and abdomen—with a five-year survival rate in the single digits. Before the trial, the patients had undergone a median of five other treatments. Three had tried checkpoint inhibitors.
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“These early TC-210 data suggest our approach may overcome the challenges faced by many T cell therapies in the hostile solid tumor microenvironment,” said Alfonso Quintás-Cardama, M.D., TCR2 chief medical officer, in a statement. “Our enrolled patients have failed multiple lines of therapy, including standard chemotherapy, checkpoint inhibitors and in some cases other mesothelin-directed approaches, in indications where survival has been historically shorter than six months.”
No patients suffered side effects in the brain, a concern with CAR-T and other T-cell therapies. Three of the five patients (60%) developed cytokine release syndrome (CRS), a condition that occurs when T-cell treatment activates the immune system too strongly. Two patients had mild CRS, but the third needed aggressive treatment. This patient also suffered lung inflammation (pneumonitis) earlier in the trial and died about a month after treatment from fungal sepsis that was deemed unrelated to the treatment.
The company plans to enroll about 50 patients in the phase 2 part of the trial, including those with non-small cell lung cancer and bile duct cancer as well as ovarian cancer and mesothelioma. Each group will have 10 patients, except the lung cancer group, which will have 20 patients. Some will receive TC-210 on its own, while the others will get TC-210 in combination with an PD-1-blocking antibody.
TCR2’s pipeline is built on its TRuC technology, which is designed to go where other engineered T-cell approaches, such as CAR-T or T-cell receptor (TCR) therapies, cannot. For example, CAR-T has seen success in some blood cancers but has faced difficulties in solid tumors. As for other engineered TCR treatments, they rely on the antigen HLA, which is downregulated in many cancers, making them invisible to T cells.
To avoid these problems, TCR2’s tech, designed by Patrick Baeuerle, Ph.D., tethers a tumor antigen-binding domain directly to the TCR complex, creating a TRuC construct that is able to recognize highly expressed tumor antigens without HLA. The full TCR is activated, which stimulates the T cell to kill the cancer cell.