TCR2Therapeutics Inc. announced positive topline results from the Phase 1 portion of the gavo-cel Phase 1/2 clinical trial for mesothelin-expressing solid tumors, with some patients still being monitored for clinical response or stable disease. 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. The patients were heavily pretreated with a median of five prior lines of therapy, including immune checkpoint inhibitors in 66% of patients and mesothelin-directed therapies in 19% of patients.

Following identification of a dose-limiting toxicity (DLT) at dose level (DL) 5 (5x108 cells/m2 following lymphodepletion) in September 2021, the study proceeded to a dose de-escalation portion, first at DL3.5 (3x108 cells/m2 following lymphodepletion) using a split-dosing approach, and subsequently at DL3 (1x108 cells/m2 following lymphodepletion) which was declared the recommended Phase 2 dose (RP2D). No new DLTs were observed. 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.

As measured by blinded independent central review (BICR), 28 of the 30 (93%) patients evaluable for efficacy experienced tumor regression of their target lesions, ranging in magnitude from 4% to 80%. Eight patients experienced target lesion regression greater than 30%, six of whom (four with mesothelioma and two with ovarian cancer) achieved a partial response (PR) according to RECIST 1.1 criteria, including one patient who also achieved a complete metabolic response. One patient with cholangiocarcinoma was also considered to have achieved a PR by investigator assessment, demonstrating that gavo-cel has induced responses in every tumor type tested to date.

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.

The primary objectives of the Phase 1 portion of the trial are to evaluate the safety profile of gavo-cel in patients whose tumors overexpress mesothelin and to determine the RP2D. Secondary objectives include ORR and DCR. Exploratory objectives include the assessment of expansion, tumor infiltration and persistence of gavo-cel.