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Aim: To determine real-world time on treatment (rwToT) with first-line pembrolizumab monotherapy for metastatic non-small-cell lung cancer (NSCLC) with programmed death ligand-1 (PD-L1) tumor proportion score (TPS) ≥50%. Methods: The Kaplan–Meier rwToT was estimated from electronic health record data for adults who initiated first-line pembrolizumab monotherapy for stage IV, PD-L1 TPS ≥50% NSCLC, with negative/unknown EGFR/ALK aberrations, and ≥6 months’ follow-up until database cutoff. Results: A total of 386 patients with ECOG 0–1 had a median rwToT of 6.9 months (95% CI: 5.6–8.3) and 12-month on-treatment rate of 36.4% (31.2–41.6) versus 40.3% (32.5–47.9) and 37.6% (31.9–43.4) in KEYNOTE-024 (KN024) and KN042 (stage IV/TPS ≥50% subpopulation), respectively. The 24-month restricted-mean rwTOT (extrapolated) was 10.5 months (9.4–11.7), versus 11.0 (9.5–12.5) and 10.4 (9.3–11.5) in KN024 and KN042, respectively. Conclusion: First-line pembrolizumab monotherapy rwToT in metastatic PD-L1 TPS ≥50% NSCLC for trial-matched patients is similar to treatment duration in KN024 and KN042.

Mass spectrometry-based platforms have gained increasing success in discovery of ligands bound to therapeutic targets as drug candidates. We established both a nanoelectrospray ionization mass spectrometry (nanoESI-MS) assay and an ultrafiltration liquid chromatography/mass spectrometry (LC/MS) assay to identify new ligands for New Delhi metallo-β-lactamase 1 (NDM-1), responsible for worldwide antibiotic resistance. To alleviate nonspecific binding of hydrophobic compounds and eliminate false positives typically encountered in the indirect LC/MS-based assay, we introduced a blocking protein in the control, which remarkably enhances the selectivity and accuracy of the indirect approach. Side-by-side comparison of the two MS-based approaches for the first time further reveals unique advantages of the indirect approach, including better reproducibility and tolerance of interference. Moreover, the success of fishing out a potent ligand from a mixture of small-molecule fragments demonstrates great potential of the indirect LC/MS-based approach for constructing a robust screening platform against combinatorial libraries or natural product extracts. More importantly, by combining the results of MS-based analyses, enzymatic activity assay, competition experiments, and structural simulation, we discovered a new compound as a promising drug candidate targeting NDM-1.

The high density of evanescent modes in the vicinity of a metal leads to enhancement of the nearfield Förster resonant energy transfer (FRET) rate. We present a classical approach to calculate the FRET rate based on the dyadic Green's function of an arbitrary dielectric environment, and consider non-local limit of material permittivity in case of metallic halfspace and thin film. In a dimer system, we find that the FRET rate is enhanced due to shared evanescent photon modes bridging a donor and an acceptor. Furthermore, a general expression for the FRET rate for multimer systems is derived. The presence of a dielectric environment and the path interference effect enhance the transfer rate, depending on the combination of distance and geometry.