Clinical trial design
MPM, pleural or peritoneal mesothelioma, cancers, NSCLC, ovarian cancer, tumor, treatment-refractory, tumors, cholangiocarcinoma
NON-SMALL CELL LUNG CANCER, OVARIAN CANCER, CANCERS, TUMOR, DISEASE, MAY, NSCLC, ONCOLOGY, TUMORS, CHOLANGIOCARCINOMA
This trial was an open-label, first-in-human, multicenter phase 1 study in patients with treatment-refractory, mesothelin-expressing cancers. The primary objective was to evaluate safety and determine the recommended phase 2 dose (RP2D) of gavo-cel. Secondary objectives included efficacy, by determining overall response rate (ORR), disease control rate (DCR), time to response (TTR) and T cell kinetics. Patients with pathologically confirmed malignant pleural or peritoneal mesothelioma (MPM), non-small cell lung cancer (NSCLC), ovarian cancer or cholangiocarcinoma were eligible if they had progressive disease despite standard of care therapy; if they had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; and if their tumors expressed mesothelin in ≥50% of tumor cells with a 2+ and/or 3+ intensity, as determined by central immunohistochemistry (IHC) assessment.Gavo-cel was infused at different dose levels (DLs) either as a single agent or after lymphodepletion (LD) with fludarabine and cyclophosphamide (Extended Data Fig. Between May 2019 and May 2022, 252 patients were screened at seven participating centers across the United States. The dates for the first and the last enrolled patients were 17 June 2019 and 28 February 2022, respectively. Of these, 58 eligible participants underwent large-volume leukapheresis, of whom 48 did so with the intent to receive a gavo-cel infusion in phase 1 (intent-to-treat (ITT) population). A gavo-cel product was manufactured for 56 of 58 apheresed patients (Fig. 