Consideration of adjusted ideal body weight dosing in BG-C9074 (B7-H4–targeting ADC) from pharmacokinetics, efficacy, and safety perspectives.

Abstract

3029 Background: B7-H4 is a transmembrane glycoprotein that is upregulated in a variety of solid tumors. BG-C9074 is an investigational topoisomerase I inhibitor antibody-drug conjugate (ADC) that targets B7-H4. We present results of the pharmacokinetic (PK) and exposure-response (ER) analyses supporting the implementation of adjusted ideal body weight (AiBW)-based dosing in the ongoing phase 1 study. Methods: BG-C9074-101 (NCT06233942) is a first-in-human, multicenter study designed to assess BG-C9074 as monotherapy and in combination with other anticancer therapies in patients (pts) with advanced solid tumors. Total body weight (TBW) and AiBW-based dosing were evaluated at 1-7 mg/kg and 6.5-9 mg/kg, respectively, administered intravenously every 3 weeks. PK samples were collected to measure serum ADC and plasma free P1021 payload analytes at Cycle 1 and steady state (Cycle 5). A population PK model, incorporating both ADC and payload, was developed and used to evaluate safety and efficacy ER relationships. Results: As of October 30, 2025, PK, safety, and efficacy data were available for 107 pts with advanced solid tumors. TBW dosing of BG-C9074 led to a maximum tolerated dose < 7 mg/kg. The ADC and free payload exposures increased with BW for TBW dosing, while ADC clearance moderately increased with BW leading to higher exposure in high BW patients (Table 1). Higher ADC exposure was associated with an increased incidence of Grade ≥3 treatment-related adverse events (TRAEs), predominantly neutropenia. Early dose modifications and use of granulocyte colony-stimulating factor were more frequent at higher doses and exposures. Increased and sustained tumor shrinkage observed in pts with ovarian cancer (OC) with higher ADC exposure. AiBW enabled a higher tolerable dose at 8 mg/kg, by normalizing ADC and payload exposure across all bodyweight ranges. Conclusions: AiBW dosing effectively reduced PK variability compared with TBW dosing, providing more consistent exposure across BW. Higher ADC exposure was associated with increased efficacy, but also with a higher incidence of manageable TRAEs. AiBW optimizes the risk-benefit profiles across BW. Clinical trial information: NCT06233942 . Underweight(<18.5 kg/m 2 ) Normal(18.5-24.9 kg/m 2 ) Overweight(25-29.9 kg/m 2 ) Obese(≥30 kg/m 2 ) Simulated Cycle 1Median ADC exposure at 7 mg/kg TBW (ng/mL) 352 464 533 626 Simulated Cycle 1 Median ADC exposure at 7 mg/kg AiBW (ng/mL) 411 448 464 481 ADC Exposure Tertile 1 2 3 Grade ≥3 TRAE 16.2% (6/37) 27.8% (10/36) 37.8% (14/37) Grade ≥3 Neutropenia 10.8% (4/37) 19.4% (7/36) 27% (10/37) Dose modifications 16.2% (6/37) 19.4% (7/36) 27% (10/37) Median tumor shrinkage in OC at Week 24 Tumor Assessment (N=25) −28.9% −33.3% −48%