Study design and patient selection
tumor, DLTs, bleeding, neutropenia, febrile neutropenia, toxicity, toxicities, thrombocytopenia, signet cell ovarian cancer, anemia, pancreatic cancer, Cancer
TUMOR, BLEEDING, FEBRILE NEUTROPENIA, ADENOCARCINOMA OF THE LUNG, CANCER, BREAST CANCER, THROMBOCYTOPENIA, SQUAMOUS CELL LUNG CANCER, NEUTROPENIC FEVER, COLON CANCER, ANEMIA, METASTATIC CANCER, PANCREATIC CANCER, CARCINOMATOSIS, DISEASE PROGRESSION, NEUTROPENIA, EVENT, DISEASE, SECONDARY, PLEURAL EFFUSIONS, INFUSION REACTION
This is a Phase I first-in-human, single center, open label, dose escalation clinical trial (NCT03476681) using a standard 3 + 3 design. The primary objective was to determine the RP2D of NEO-201. The secondary objective was to assess the preliminary antitumor activity of NEO-201 and exploratory aims characterized the tumor expression of NEO-201 target antigen in archival tumor tissue, pharmacokinetics (PK), immunogenicity and effects of NEO-201 on immunologic correlates, including functional and phenotypic immune response and serum cytokines, chemokines, and soluble factors. All patients in this open-label study were treated at the National Cancer Institute (NCI), National Institutes of Health (NIH), USA. At each dose level, groups of 3–6 patients received NEO-201 intravenously at doses ranging from 1.0 to 2.0 mg/kg every 2 weeks until unacceptable toxicity, patient withdrawal or disease progression. Cycles were 28 days in length.Dose-limiting toxicities (DLTs) were defined as neutropenic fever, grade 4 neutropenia or thrombocytopenia lasting > 7 days, grade 3 thrombocytopenia with bleeding, or any grade 3 or higher NEO-201–related event occurring during the first cycle. As discussed below, the study was subsequently amended to recognize neutropenia as an expected toxicity, and grade 3 neutropenia improving to grade ≤ 2 with supportive growth factor therapy by the next scheduled dose or grade 3 febrile neutropenia improving within 72 h with or without interventions were not considered DLTs. Other exceptions that were not considered DLTs included transient infusion reactions resolving to grade 1 or better in less than 8 h, and grade 3 anemia less than 2 mg/dL below baseline or resolving to grade 1 or baseline by next scheduled dose. Full DLT definition is provided in the protocol in the supplementary materials. The MTD was defined as the highest dose at which fewer than two of six patients experienced a DLT. At the conclusion of the 2Based on previously conducted tissue reactivity studies described above, the dose escalation phase of this trial was opened to tumor types in which reactivity occurred in the majority of samples, including colon cancer, pancreatic cancer, adenocarcinoma of the lung, squamous cell lung cancer, breast cancer, and mucinous and signet cell ovarian cancer. Additional key eligibility criteria included locally advanced or metastatic cancer not eligible for standard therapy known to confer clinical benefit, disease that was measurable by RECIST v1.1 criteria or otherwise evaluable (e.g. bone scan, peritoneal or pleural effusions, carcinomatosis), and adequate performance status (e.g. ECOG ≤ 2 or Karnofsky ≥ 50%). There was no limit on number of prior therapies, including immunotherapies.