27 июля 2020
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TCR2 Therapeutics announces interim data for Phase 1 of TC-210 trial
TCR2 Therapeutics объявляет промежуточные данные для Фазы 1 испытания TC-210
TCR2 Therapeutics announced interim data from the first five patients treated in the Phase 1 portion of the TC-210 Phase 1/2 clinical trial for mesothelin-expressing solid tumors. All five patients showed tumor regression including two RECIST unconfirmed partial responses - one of which remains subject to independent central review - and two patients with stable disease through six months. Translational data further demonstrated TRuC-T cell expansion and activation. A manageable toxicity profile was observed with only one patient exhibiting TC-210-related non-hematologic grade greater than 2 toxicity and no evidence of neurotoxicity or on-target, off-tumor toxicity. The primary objectives of the Phase 1 portion of the study are to define the safety profile of TC-210 in patients whose tumors overexpress mesothelin and to determine the recommended Phase 2 dose. Secondary objectives include overall response rate and disease control rate. Exploratory objectives include the assessment of expansion, tumor infiltration, and persistence of TC-210 T cells. TC-210 was generally well tolerated, with no patients experiencing neurotoxicity or on-target, off-tumor toxicities. Three patients experienced Cytokine Release Syndrome, which was Grade 1 in two patients and Grade 3 in one patient. The patient experiencing Grade 3 CRS also developed Grade 3 pneumonitis during the first week post infusion that responded to tocilizumab and steroid therapy. This patient died 34 days post treatment due to fungal sepsis, which was deemed unrelated to TC-210. Because of the earlier pneumonitis event, however, the Safety Review Team recommended the expansion of the cohort from three to six patients. None of the subsequent three patients treated at DL1 developed pneumonitis or CRS above Grade 1. All five patients treated with TC-210 T cells have had at least one disease response assessment. The DCR was 100%, with all patients experiencing tumor regression. The median change in the sum of diameters of target lesions was -42%. The ORR was 40% according to RECIST v1.1. TC-210 therapy induced a significant reduction in FDG uptake by PET imaging in two evaluable patients, including one patient who achieved a complete metabolic response. The Phase 1/2 clinical trial is evaluating the safety and efficacy of TC-210, TCR2's T-cell receptor fusion construct directed against mesothelin. The trial is enrolling patients with mesothelin expressing NSCLC, ovarian cancer, cholangiocarcinoma, and malignant pleural/peritoneal mesothelioma. The Phase 1 dose escalation portion of the clinical trial utilizes a modified 3+3 design with four increasing TC-210 T cell doses. At each dose, TC-210 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. In the Phase 2 portion of the clinical trial, approximately 50 patients are planned to receive TC-210 at the RP2D in four distinct cohorts according to their cancer diagnosis: NSCLC, ovarian cancer, malignant pleural/peritoneal mesothelioma and cholangiocarcinoma. Each cohort will include ten patients, except the NSCLC cohort which will include 20 patients with eight patients to receive TC-210 as single agent and 12 patients to receive TC-210 in combination with a programmed cell death 1 blocking antibody.