TCR2Therapeutics Inc. announced positive interim results from the ongoing Phase 1 portion of the gavo-cel Phase 1/2 clinical trial for mesothelin-expressing solid tumors. As of the June 30, 2021 data cutoff, 17 patients (12 mesothelioma, 4 ovarian cancer and 1 cholangiocarcinoma) had received a single gavo-cel infusion in the dose escalation portion of the gavo-cel Phase 1 clinical trial. The median number of prior lines of therapy was 5, including immune checkpoint inhibitors (n=11) and mesothelin-directed therapies (n=5). Gavo-cel was administered up to dose level 5 (DL5) (5x108/m2 following lymphodepletion). Two dose limiting toxicities were reported: one Grade 3 pneumonitis at DL1 that resolved with supportive measures, which permitted the continuation of dose escalation, and one Grade 5 bronchoalveolar hemorrhage at DL5, which along with the development of severe CRS in all 3 patients treated at this dose level, led the Safety Review Team to declare 5x108/m2 as the MTD. Following identification of the MTD, one patient has received gavo-cel at 3x108/m2 after lymphodepletion using a split dosing approach to refine the RP2D and an additional patient has been treated at DL3 (1x108/m2 following lymphodepletion). In both cases gavo-cel was well tolerated with only Grade 1 non-hematological toxicities being reported. 15 of the 16 patients evaluable for efficacy experienced regression of their target lesions, ranging in magnitude from 5% to 75%. Six patients achieved partial responses (PRs) by target lesion assessment, four of whom (3 with mesothelioma and 1 with ovarian cancer) achieved a PR according to RECIST 1.1 criteria, including one who also achieved a complete metabolic response. One patient with cholangiocarcinoma was also considered to have achieved a PR by investigator assessment, for an ORR of 31%. By independent review assessment, the ORR was 25% with a DCR Rate of 81%. The median overall survival for patients with mesothelioma is 11.2 months, whereas the median progression free survival is 5.9 months. The primary objectives of the Phase 1 portion of the trial are to define 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. Summary of trial conduct, baseline characteristics and gavo-celdose: Screening: 46% of patients met the mesothelin expression cut-off as defined per protocol. Patient Characteristics: 17 patients received gavo-cel including 12 with mesothelioma, 4 with ovarian cancer and 1 with cholangiocarcinoma with a median age of 57 years (range, 31-84 years). The median number of prior therapies was 5 (range, 1-9), including immune checkpoint inhibitor therapy (n=11) and anti-mesothelin therapies (n=5). Gavo-cel Dose: The seventeen patients disclosed to date have received gavo-cel at the following dose level (DL): DL 0: 5x107 cells/m2 without lymphodepletion 1 mesothelioma patient DL 1: 5x107 cells/m2 following lymphodepletion 5 mesothelioma patients and 1 ovarian cancer patient DL 2: 1x108 cells/m2 without lymphodepletion 1 mesothelioma patient DL 3: 1x108 cells/m2 following lymphodepletion 1 mesothelioma patient, 1 cholangiocarcinoma patient, and 3 ovarian cancer patients DL 4: 5x108 cells/m2 without lymphodepletion 1 mesothelioma patient DL 5: 5x108 cells/m2 following lymphodepletion 3 mesothelioma patients Key clinical findings from patients treated with gavo-cel: Safety: gavo-cel was generally well tolerated with a manageable adverse event profile with no patients experiencing on-target, off-tumor toxicities. Two DLTs were observed: one case of Grade 3 pneumonitis at DL1 that resolved with anti-cytokine therapy, and one case of Grade 5 bronchoalveolar hemorrhage at DL5. Furthermore, all three patients treated at DL5 experienced Grade =3 CRS which resulted in 5x108 cells/m2 following lymphodepletion being declared the MTD. Clinical Activity: 16 patients were evaluable for response. Tumor regression was observed in 15 (94%) patients with a DCR of 81%. Six patients achieved partial responses (PRs) by target lesion assessment, four of whom (3 with mesothelioma and 1 with ovarian cancer) achieved a PR according to RECIST 1.1 criteria. The ORR by RECISTv1.1 criteria among patients infused with gavo-cel following lymphodepletion chemotherapy was 31% by independent review assessment, including one patient who achieved a complete metabolic response, and 38% by investigator assessment, which included a PR in a patient with metastatic cholangiocarcinoma. Translational Data: Peak gavo-cel expansion (Cmax) increased when gavo-cel was administered following lymphodepletion in a dose dependent fashion. Cytokine elevations post-gavo-cel infusion were observed in all evaluable patients, which is indicative of mesothelin target engagement. The Phase 1/2 clinical trial (NCT03907852) is evaluating the safety and efficacy of gavocabtagene autoleucel (gavo-cel; TC-210), TCR2s T cell receptor fusion construct directed against mesothelin. The trial is enrolling patients with either mesothelin expressing non-small cell lung cancer (NSCLC), ovarian cancer, cholangiocarcinoma, or malignant pleural/peritoneal mesothelioma. The Phase 1 dose escalation portion of the clinical trial utilizes a modified 3+3 design with four increasing gavo-cel doses. At each dose, gavo-cel will be tested in two separate dose levels: first without lymphodepletion and then following lymphodepleting chemotherapy. The Phase 1 portion of the clinical trial is ongoing.