Insilico Medicine reported first-in-human Phase 1 results for ISM6331 in mesothelioma, showing a 40.0% objective response rate at the 130 mg once-daily dose and 18.2% across all dose levels, with a 68.2% disease control rate. No dose-limiting toxicities were observed from 15 mg to 130 mg, and sustained reductions in circulating CCN2 confirmed target engagement. The pharmacokinetic profile, with a terminal half-life of 18–32 hours, supports once-daily oral dosing.
Key Points
- 40% response rate at 130 mg in evaluable mesothelioma patients
- No dose-limiting toxicities across 15–130 mg dose range
- Circulating CCN2 reductions confirm sustained target engagement
Longevity Analysis
Mesothelioma remains among the most treatment-resistant malignancies, and a tolerable oral agent producing durable responses in heavily pretreated patients — median two prior lines, up to twelve — addresses a population with few remaining options. The use of circulating CCN2 as a pharmacodynamic readout demonstrates how measurable signals can guide dose selection rather than relying on tolerability ceilings alone, an approach with application well beyond oncology. Once-daily dosing with low-grade, reversible adverse events matters practically: sustained benefit depends on a regimen patients can maintain over months, not weeks.
Original published by LT Wire.