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|Ref Type||Journal Article|
|Authors||Kato H, de Souza P, Kim SW, Lickliter JD, Naito Y, Park K, Kumar S, Mugundu GM, Bang YJ|
|Title||Safety, Pharmacokinetics, and Clinical Activity of Adavosertib in Combination with Chemotherapy in Asian Patients with Advanced Solid Tumors: Phase Ib Study.|
|Abstract Text||The WEE1 inhibitor adavosertib (AZD1775) has been investigated in Western patients.This open-label Phase Ib study (NCT02341456) investigated the safety, pharmacokinetics, and clinical activity of adavosertib in combination with carboplatin alone or paclitaxel plus carboplatin in Asian patients with advanced solid tumors and defined the recommended Phase II dose.Nineteen patients received adavosertib 175 mg twice daily (bid) for 2.5 days (five doses) in combination with carboplatin (AUC 5) alone or paclitaxel (175 mg/m2) plus carboplatin, or adavosertib 225 mg bid for 2.5 days in combination with paclitaxel plus carboplatin in 21-day cycles. Preliminary safety and dose-limiting toxicity analyses were performed and dose escalation/de-escalation conducted as appropriate.Adavosertib 175 mg bid for 2.5 days with carboplatin alone or paclitaxel plus carboplatin was considered tolerable. Two patients receiving adavosertib 225 mg bid in combination with paclitaxel plus carboplatin experienced dose-limiting toxicities (grade 4 sepsis; grade 5 acute respiratory distress syndrome); this regimen was not considered tolerable. Grade ≥ 3 adverse events reported most commonly in any cohort included: anemia; decreased white blood cell count; decreased neutrophil count; neutropenia; decreased platelet count; thrombocytopenia; and febrile neutropenia. Exposure to adavosertib, as determined by pharmacokinetic analysis, in Asian patients was higher than that previously seen in Western patients. A partial response occurred in 2/12 evaluable patients (16.7%) at the recommended Phase II dose.Adavosertib 175 mg bid for 2.5 days was chosen as the recommended Phase II dose in combination with paclitaxel and carboplatin in Asian patients.|
|Molecular Profile||Treatment Approach|
|Gene Name||Source||Synonyms||Protein Domains||Gene Description||Gene Role|
|Therapy Name||Drugs||Efficacy Evidence||Clinical Trials|
|Drug Name||Trade Name||Synonyms||Drug Classes||Drug Description|
|Gene||Variant||Impact||Protein Effect||Variant Description||Associated with drug Resistance|
|Molecular Profile||Indication/Tumor Type||Response Type||Therapy Name||Approval Status||Evidence Type||Efficacy Evidence||References|
|Unknown unknown||Advanced Solid Tumor||not applicable||Adavosertib + Carboplatin + Paclitaxel||Phase Ib/II||Actionable||In a Phase Ib trial, treatment with Adavosertib (MK-1775) in combination with Paraplatin (carboplatin) and Taxol (paclitaxel) at the recommended Phase II does was tolerable and resulted in partial response in 16.7% (1/3) of patients and stable disease in 33.3% (2/6) of Asian patients with advanced solid tumors (PMID: 32034630).||32034630|
|Unknown unknown||Advanced Solid Tumor||not applicable||Adavosertib + Carboplatin||Phase Ib/II||Actionable||In a Phase Ib trial, Adavosertib (MK-1775) in combination with Paraplatin (carboplatin) was tolerable and resulted in partial response in 16.7% (1/3) of patients and stable disease in 33.3% (2/6) of Asian patients with advanced solid tumors (PMID: 32034630).||32034630|