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Item KEYNOTE-033: Randomized phase 3 study of pembrolizumab vs docetaxel in previously treated, PD-L1-positive, advanced NSCLC(International Journal of Cancer, 2023) Ren, S.; Feng, J.; Ma, S.; Chen, H.; Ma, Z.; Huang, C.; Zhang, L.; He, J.; Wang, C.; Zhou, J.; Danchaivijitr, P.; Wang, C.-C.; Винниченко, Ігор Олександрович; Vynnychenko, Ihor Oleksandrovych; Wang, K.; Orlandi, F.; Sriuranpong, V.; Li, B.; Ge, J.; Dang, T.; Zhou, C.KEYNOTE-033 (NCT02864394) was a multicountry, open-label, phase 3 study that compared pembrolizumab vs docetaxel in previously treated, programmed death- ligand 1 (PD-L1)-positive, advanced non-small cell lung cancer (NSCLC), with most patients enrolled in mainland China. Eligible patients were randomized (1:1) to pem- brolizumab 2 mg/kg or docetaxel 75 mg/m2 every 3 weeks. Primary endpoints were overall survival (OS) and progression-free survival and were evaluated sequentially using stratified log-rank tests, first in patients with PD-L1 tumor proportion score (TPS) ≥50% and then in patients with PD-L1 TPS ≥1% (significance threshold: P < .025, one-sided). A total of 425 patients were randomized to pembrolizumab (N = 213) or docetaxel (N = 212) between 8 September 2016 and 17 October 2018. In patients with a PD-L1 TPS ≥50% (n = 227), median OS was 12.3 months with pembrolizumab and 10.9 months with docetaxel; the hazard ratio (HR) was 0.83 (95% confidence interval [CI]: 0.61-1.14; P = .1276). Because the significance threshold was not met, sequential testing of OS and PFS was ceased. In patients with a PD-L1 TPS ≥1%, the HR for OS for pembrolizumab vs docetaxel was 0.75 (95% CI: 0.60-0.95). In patients from mainland China (n = 311) with a PD-L1 TPS ≥1%, HR for OS was 0.68 (95% CI: 0.51-0.89). Incidence of grade 3 to 5 treatment- related AEs was 11.3% with pembrolizumab vs 47.5% with docetaxel. In summary, pembrolizumab improved OS vs docetaxel in previously treated, PD-L1-positive NSCLC without unexpected safety signals; although the statistical significance threshold was not reached, the numerical improvement is consistent with that pre- viously observed for pembrolizumab in previously treated, advanced NSCLC.Item Fluorophore-conjugated Helicobacter pylori recombinant membrane protein (HopQ) labels primary colon cancer and metastases in orthotopic mouse models by binding CEA-related cell adhesion molecules(Elsevier Inc. on behalf of Neoplasia Press, Inc., 2020) Hollandsworth, H.M.; Schmitt, V.; Amirfakhri, S.; Filemoni, F.; Schmidt, A.; Landström, М.; Линдін, Микола Сергійович; Лындин, Николай Сергеевич; Lyndin, Mykola Serhiiovych; Backert, S.; Gerhard, M.; Wennemuth, G.; Hoffman, R.M.; Singer, B.B.; Bouvet, M.HopQ is an outer-membrane protein of Helicobacter pylori that binds to human carcinoembryonic antigen-related celladhesion molecules (CEACAMs) with high specificity. We aimed to investigate fluorescence targeting of CEACAMexpressing colorectal tumors in patient-derived orthotopic xenograft (PDOX) models with fluorescently labeled recombinant HopQ (rHopQ). Western blotting, flow cytometry and ELISA were performed to determine the efficiency of rHopQ binding to CEACAMs. rHopQ was conjugated to IR800DyeCW (rHopQ IR800). Nude mice received orthotopic implantation of colon cancer tumors. Three weeks later, mice were administered 25 μg or 50 μg HopQ-IR800 and imaged 24 or 48 h later. Intravital images were analyzed for tumor-to-background ratio (TBR). Flow cytometry and ELISA demonstrated binding of HopQ to CEACAM1, 3 and 5. Dose-response intravital imaging in PDOX models demonstrated optimal results 48 h after administration of 50 μg rHopQ-IR800 (TBR = 3.576) in our protocol. Orthotopic models demonstrated clear tumor margins of primary tumors and small regional metastases with a mean TBR = 3.678 (SD ± 1.027). rHopQ showed specific binding to various CEACAMs in PDOX models. rHopQ may be useful for CEACAM-positive tumor and metastasis detection for pre-surgical diagnosis, intra-operative imaging and fluorescence-guided surgery.