التفاصيل البيبلوغرافية
| العنوان: |
Phase 1 study of the ATR inhibitor berzosertib (formerly M6620, VX-970) combined with gemcitabine ± cisplatin in patients with advanced solid tumours. |
| المؤلفون: |
Middleton, Mark R., Dean, Emma, Evans, Thomas R. J., Shapiro, Geoffrey I., Pollard, John, Hendriks, Bart S., Falk, Martin, Diaz-Padilla, Ivan, Plummer, Ruth |
| المصدر: |
British Journal of Cancer; Aug2021, Vol. 125 Issue 4, p510-519, 10p |
| مصطلحات موضوعية: |
RESEARCH, HETEROCYCLIC compounds, RESEARCH methodology, DEOXYCYTIDINE, ANTINEOPLASTIC agents, MEDICAL cooperation, EVALUATION research, TREATMENT effectiveness, DRUG administration, COMPARATIVE studies, CISPLATIN, SURVIVAL analysis (Biometry), TUMORS |
| مستخلص: |
Background: Berzosertib (formerly M6620, VX-970) is a highly potent and selective, first-in-class inhibitor of ataxia telangiectasia and Rad3-related protein kinase (ATR). We assessed multiple ascending doses of berzosertib + gemcitabine ± cisplatin in patients with resistant/refractory advanced solid tumours.Methods: We evaluated the safety, tolerability, pharmacokinetics (PK) and preliminary efficacy of intravenous berzosertib + gemcitabine ± cisplatin using a standard 3 + 3 dose-escalation design. The starting doses were berzosertib 18 mg/m2, gemcitabine 875 mg/m2 and cisplatin 60 mg/m2.Results: Fifty-two patients received berzosertib + gemcitabine and eight received berzosertib + gemcitabine + cisplatin. Four patients receiving berzosertib + gemcitabine had a total of seven dose-limiting toxicities (DLTs) and three receiving berzosertib + gemcitabine + cisplatin had a total of three DLTs. Berzosertib 210 mg/m2 (days 2 and 9) + gemcitabine 1000 mg/m2 (days 1 and 8) Q3W was established as the recommended Phase 2 dose (RP2D); no RP2D was determined for berzosertib + gemcitabine + cisplatin. Neither gemcitabine nor cisplatin affected berzosertib PK. Most patients in both arms achieved a best response of either partial response or stable disease.Conclusions: Berzosertib + gemcitabine was well tolerated in patients with advanced solid tumours and showed preliminary efficacy signs.Clinical Trial Identifier: NCT02157792. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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