Oral exposure was linear across the 10‑30 mg kg⁻¹ dose range. No accumulation observed after 7 days of qd dosing.
| Technique | Instrument | Conditions | |-----------|------------|------------| | Surface Plasmon Resonance (SPR) | Biacore T200 | PD‑L1 immobilized (500 RU), 25 °C, 0.1 M HEPES pH 7.4 | | Isothermal Titration Calorimetry (ITC) | MicroCal PEAQ‑ITC | 20 °C, 10 µM PD‑1, 100‑µM ADN‑388 | | Differential Scanning Fluorimetry (DSF) | CFX96 (Bio‑Rad) | 0.5 µM PD‑L1, 10‑µM SYPRO‑Orange | adn-388
PK parameters (C max , AUC 0‑∞ , t ½ , clearance, volume of distribution) were derived using non‑compartmental analysis (Phoenix WinNonlin). Oral exposure was linear across the 10‑30 mg
Treatment initiated when tumors reached ~80 mm³. Groups (n = 10 per arm): vehicle, ADN‑388 (10 mg kg⁻¹ qd), ADN‑388 (30 mg kg⁻¹ qd), anti‑PD‑1 mAb (10 mg kg⁻¹, i.p., q3d), and combination ADN‑388 + low‑dose cyclophosphamide (50 mg kg⁻¹, i.p., weekly). Tumor volumes measured thrice weekly; TGI calculated at day 21. Treatment initiated when tumors reached ~80 mm³
The development of ADN-388 presents a promising new treatment option for patients with c-MET-driven cancers. The potential benefits of ADN-388 include: