Phase 1 study of ceralasertib, an ATR kinase inhibitor, in combination with durvalumab in patients with recurrent or metastatic NSCLC or HNSCC - PubMed
18 hours ago
- #ATR inhibitor
- #Phase 1 trial
- #Immunotherapy combination
- This Phase 1 study evaluated the ATR inhibitor ceralasertib combined with PD-L1 inhibitor durvalumab in advanced/metastatic NSCLC or HNSCC patients.
- Safety and tolerability were the primary objectives, with doses of ceralasertib ranging from 80 mg BID to 320 mg QD.
- Two dose-limiting toxicities occurred: Grade 3 thrombocytopenia with anemia (320 mg QD) and Grade 4 thrombocytopenia with neutropenia (240 mg BID).
- 98.3% of patients experienced treatment-emergent adverse events, and 51.7% had grade ≥3 events.
- The recommended Phase 2 dose is durvalumab 1500 mg on Day 1 plus ceralasertib 240 mg BID from Days 15-28.
- Objective responses were seen in 8.3% of patients, and 51.7% had stable disease.
- Pharmacodynamic activity (pRAD50 increase) was observed in 10 out of 14 paired biopsies.
- The combination was tolerated and showed antitumor activity in these advanced cancers.