Phase 1 study of ceralasertib, an ATR kinase inhibitor, in combination with durvalumab in patients with recurrent or metastatic NSCLC or HNSCC.
1/5 보강
PICO 자동 추출 (휴리스틱, conf 2/4)
유사 논문P · Population 대상 환자/모집단
환자: previously treated advanced/metastatic non-small-cell lung cancer (NSCLC) or head and neck squamous cell carcinoma (HNSCC)
I · Intervention 중재 / 시술
추출되지 않음
C · Comparison 대조 / 비교
추출되지 않음
O · Outcome 결과 / 결론
[CONCLUSION] Ceralasertib plus durvalumab was tolerated and associated with antitumour activity in advanced/metastatic NSCLC and HNSCC. [TRIAL REGISTRATION NUMBER] NCT02264678.
[BACKGROUND] This multicentre, modular, Phase 1 study evaluated escalating doses of ATR (ataxia telangiectasia and Rad3-related kinase) inhibitor ceralasertib plus PD-L1 inhibitor durvalumab in patien
APA
Lopez JS, Harrington KJ, et al. (2026). Phase 1 study of ceralasertib, an ATR kinase inhibitor, in combination with durvalumab in patients with recurrent or metastatic NSCLC or HNSCC.. British journal of cancer. https://doi.org/10.1038/s41416-026-03408-y
MLA
Lopez JS, et al.. "Phase 1 study of ceralasertib, an ATR kinase inhibitor, in combination with durvalumab in patients with recurrent or metastatic NSCLC or HNSCC.." British journal of cancer, 2026.
PMID
41917211
Abstract
[BACKGROUND] This multicentre, modular, Phase 1 study evaluated escalating doses of ATR (ataxia telangiectasia and Rad3-related kinase) inhibitor ceralasertib plus PD-L1 inhibitor durvalumab in patients with previously treated advanced/metastatic non-small-cell lung cancer (NSCLC) or head and neck squamous cell carcinoma (HNSCC).
[METHODS] Patients received ceralasertib 80/160/240 mg twice-daily (BID) or 320 mg once-daily (QD) for 7 (Days 22-28) or 14 (Days 15-28) days, plus durvalumab 1500 mg (Day 1), per 28-day cycle. The primary objective was to investigate the safety/tolerability of the combination.
[RESULTS] Sixty patients were treated. Two patients had dose-limiting toxicities of: Grade 3 thrombocytopenia with Grade 3 anaemia (ceralasertib 320 mg QD for 14 days); and Grade 4 thrombocytopenia with Grade 3 neutropenia accompanied by systemic chest infection (ceralasertib 240 mg BID for 14 days). Overall, 59 (98.3%) patients had treatment-emergent adverse events; 31 (51.7%) had grade ≥3 events. The recommended Phase 2 dose was durvalumab 1500 mg (Day 1) plus ceralasertib 240 mg BID (Days 15-28). Five (8.3%) patients had objective responses; 31 (51.7%) had stable disease. Pharmacodynamic activity (pRAD50 increase) was observed in 10/14 paired biopsies.
[CONCLUSION] Ceralasertib plus durvalumab was tolerated and associated with antitumour activity in advanced/metastatic NSCLC and HNSCC.
[TRIAL REGISTRATION NUMBER] NCT02264678.
[METHODS] Patients received ceralasertib 80/160/240 mg twice-daily (BID) or 320 mg once-daily (QD) for 7 (Days 22-28) or 14 (Days 15-28) days, plus durvalumab 1500 mg (Day 1), per 28-day cycle. The primary objective was to investigate the safety/tolerability of the combination.
[RESULTS] Sixty patients were treated. Two patients had dose-limiting toxicities of: Grade 3 thrombocytopenia with Grade 3 anaemia (ceralasertib 320 mg QD for 14 days); and Grade 4 thrombocytopenia with Grade 3 neutropenia accompanied by systemic chest infection (ceralasertib 240 mg BID for 14 days). Overall, 59 (98.3%) patients had treatment-emergent adverse events; 31 (51.7%) had grade ≥3 events. The recommended Phase 2 dose was durvalumab 1500 mg (Day 1) plus ceralasertib 240 mg BID (Days 15-28). Five (8.3%) patients had objective responses; 31 (51.7%) had stable disease. Pharmacodynamic activity (pRAD50 increase) was observed in 10/14 paired biopsies.
[CONCLUSION] Ceralasertib plus durvalumab was tolerated and associated with antitumour activity in advanced/metastatic NSCLC and HNSCC.
[TRIAL REGISTRATION NUMBER] NCT02264678.