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We report the population pharmacokinetic (PK) and exposure-response analyses of a novel subcutaneous formulation of daratumumab (DARA) using data from 3 DARA subcutaneous monotherapy studies (PAVO Part 2, MMY1008, COLUMBA) and 1 combination therapy study (PLEIADES). Results were based on 5159 PK samples from 742 patients (DARA 1800 mg subcutaneously, n = 487 [monotherapy, n = 288; combination therapy, n = 199]; DARA 16 mg/kg intravenously, n = 255 [all monotherapy, in COLUMBA]; age, 33-92 years; weight, 28.6-147.6 kg). Subcutaneous and intravenous DARA monotherapies were administered once every week for cycles 1-2, once every 2 weeks for cycles 3-6, and once every 4 weeks thereafter (1 cycle is 28 days). The subcutaneous DARA combination therapy was administered with the adaptation of corresponding standard-of-care regimens. PK samples were collected between cycle 1 and cycle 12. Among monotherapy studies, throughout the treatment period, subcutaneous DARA provided similar/slightly higher trough concentrations (Ctrough ) versus intravenous DARA, with lower maximum concentrations and smaller peak-to-trough fluctuations. The PK profile was consistent between subcutaneous DARA monotherapy and combination therapies. The exposure-response relationship between daratumumab PK and efficacy or safety end points was similar for subcutaneous and intravenous DARA. Although the ≤65-kg subgroup reported a higher incidence of neutropenia, no relationship was found between the incidence of neutropenia and exposure, which was attributed, in part, to the preexisting imbalance in neutropenia between subcutaneous DARA (45.5%) and intravenous DARA (19%) in patients ≤50 kg. A flat relationship was observed between body weight and any grade and at least grade 3 infections. The results support the DARA 1800-mg subcutaneous flat dose as an alternative to the approved intravenous DARA 16 mg/kg.

The present switching speed measurement devices for circuit breakers are mostly low in accuracy， severe on installation conditions， and cannot achieve real-time online monitoring. A new system for real-time switching speed measurement of circuit breakers based on a line array camera is proposed. First， the experimental technique is studied by building an experimental frame simulating the rotation of circuit breakers. A turntable is installed at the output of the motor to simulate the rotating shaft of the circuit breaker actuator， and a line array camera is placed on the turntable side to capture the black and white narrow strip images of the targets set on the turntable. Afterward， the appropriate resolution， exposure time and judgment threshold are chosen to analyze the changes of the images taken by the line array camera in real time to obtain the real-time motion travel of the target and the rotation speed of the turntable. The switching speed of the circuit breaker is obtained to verify the feasibility of the measurement scheme. Finally， it is applied to a pilot substation to monitor the motion travel of the switching of the circuit breaker in real time. Compared with the existing technology， this measurement system can process the images more quickly and measure the switching speed more precisely and stably.

Amivantamab has demonstrated durable responses with a tolerable safety profile in non‐small cell lung cancer with EGFR exon 20 insertions (Ex20ins) who progressed after prior platinum chemotherapy. Data supporting the amivantamab recommended phase II dose (RP2D) in this patient population are presented. Pharmacokinetic (PK) analysis and population PK (PopPK) modeling were conducted using serum concentration data obtained following amivantamab intravenous administration (140–1,750 mg). Pharmacodynamics (PDs) were evaluated using depletion of soluble EGFR and MET. Exposure‐response (E‐R) analyses were performed using the primary efficacy end point of objective response rate in patients with EGFR Ex20ins. The E‐R relationship for safety was explored for adverse events of clinical interest. Amivantamab exhibited linear PKs at 350–1,750 mg dose levels following administration, with no maximum tolerated dose identified. A two‐compartment PopPK model with linear clearance adequately described the observed PKs. Body weight was a covariate of clearance and volume of distribution in the central compartment. PopPK modeling showed that a weight‐based, 2‐tier (< 80 and ≥ 80 kg) dosing strategy reduces PK variability and provides comparable exposure across 2 weight groups, with 87% of patients achieving exposures above the target threshold. The final confirmed RP2D of amivantamab was 1,050 mg for < 80 kg (1,400 mg for ≥ 80 kg) weekly in cycle 1 (28 days) and every 2 weeks thereafter. No significant exposure‐efficacy or safety correlation was observed. In conclusion, the amivantamab RP2D is supported by PK, PD, safety, and efficacy analyses. E‐R analyses confirmed that the current regimen provides durable efficacy with tolerable safety. [ABSTRACT FROM AUTHOR]

The article introduces the new Editor-in-Chief and three Associate Editors for The Journal of Clinical Pharmacology, highlighting the goal of expanding the journal's visibility and fostering intradisciplinary collaboration. Topics include the emphasis on global outreach, increased publication of state-of-the-art reviews and editorials, and a commitment to supporting Early Stage Professionals in the field of clinical pharmacology.