British journal of cancer · 2026
Phase 1 study of ceralasertib, an ATR kinase inhibitor, in combination with durvalumab in patients with recurrent or metastatic NSCLC or HNSCC.
СтатьяКлиническое исследование I фазыМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Lopez Juanita S, Harrington Kevin J, Im Seock-Ah, Lee Keun-Wook, Postel-Vinay Sophie, Thomas Jacob S, Lukashchuk Natalia, Willis Sophie E, Irurzun-Arana Itziar, Webb Benjamin, Nehra Jyoti, Lau Alan, Loembé Arsène-Bienvenu, Dean Emma, Krebs Matthew G
Аннотация
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.
Предметные рубрики MeSH
AdultAgedAged, 80 and overFemaleHumansMaleMiddle AgedAntibodies, MonoclonalAntineoplastic Combined Chemotherapy ProtocolsCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellHead and Neck NeoplasmsIndolesLung NeoplasmsNeoplasm MetastasisNeoplasm Recurrence, LocalProtein Kinase InhibitorsPteridinesPyrazinesPyrazolesPyrimidinesPyrrolesSquamous Cell Carcinoma of Head and NeckMorpholinesSulfonamidesAtaxia Telangiectasia Mutated Proteins