Therapy Detail

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Therapy Name Adavosertib
Synonyms
Therapy Description

Adavosertib (MK-1775) is a small molecule inhibitor of the tyrosine kinase WEE1 with potential antineoplastic sensitizing activity (PMID: 22084170).

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Drug Name Trade Name Synonyms Drug Classes Drug Description
Adavosertib MK-1775|AZD1775|AZ1775 WEE1 Inhibitor 5 Adavosertib (MK-1775) is a small molecule inhibitor of the tyrosine kinase WEE1 with potential antineoplastic sensitizing activity (PMID: 22084170, PMID: 32611648).

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
TP53 loss Advanced Solid Tumor sensitive Adavosertib Preclinical Actionable In a preclinical study, tumor cell lines carrying deficient TP53 were sensitized to DNA-damaging agents upon Adavosertib (MK-1775) administration (PMID: 19887545). 19887545
TP53 mutant glioblastoma sensitive Adavosertib Preclinical - Pdx Actionable In a preclinical study, treatment with Adavosertib (MK-1775) decreased CDK1 phosphorylation and reduced tumor growth in patient-derived xenograft models of glioblastoma multiforme that harbor TP53 mutations (PMID: 27196784). 27196784
TP53 mutant endometrial carcinoma predicted - sensitive Adavosertib Case Reports/Case Series Actionable In a Phase I trial, Adavosertib (MK-1775) treatment resulted in a partial response (PR) in 17% (6/35) of patients with advanced solid tumors, 2 of the patients achieved PR had endometrial carcinoma (EC), and TP53 mutations were identified in 1 of the EC patients with biopsy available for genomic analysis (J Clin Oncol 38: 2020 (suppl; abstr 3624); NCT01748825). detail...
TP53 mutant ovarian carcinoma predicted - sensitive Adavosertib Case Reports/Case Series Actionable In a Phase I trial, Adavosertib (MK-1775) treatment resulted in a partial response (PR) in 17% (6/35) of patients with advanced solid tumors, 4 of the patients achieved PR had ovarian carcinoma (OVC), and TP53 mutations were identified in 2 of the OVC patients with biopsies available for genomic analysis (J Clin Oncol 38: 2020 (suppl; abstr 3624); NCT01748825). detail...
KIT exon 11 del gastrointestinal stromal tumor no benefit Adavosertib Preclinical - Cell line xenograft Actionable In a preclinical study, Adavosertib (MK-1775) treatment resulted in reduced cell viability of gastrointestinal stromal tumor cells harboring a KIT exon 11 deletion in culture, but did not lead to improved tumor growth inhibition or prolonged survival compared to controls in cell line xenograft models (PMID: 33320833). 33320833
TP53 mutant esophagus squamous cell carcinoma predicted - sensitive Adavosertib Preclinical - Cell culture Actionable In a preclinical study, Adavosertib (MK-1775) treatment inhibited viability of TP53-mutant esophageal squamous cell carcinoma cells in culture (PMID: 32220892). 32220892
NRAS mutant melanoma sensitive Adavosertib Preclinical Actionable In a preclinical study, Adavosertib (MK-1775) showed efficacy in NRAS mutant melanoma and in mutant KRAS colorectal, pancreatic, and lung cancers (PMID: 24791855). 24791855
TP53 mutant Advanced Solid Tumor predicted - sensitive Adavosertib Phase I Actionable In a retrospective analysis of a Phase I trial, Adavosertib (MK-1775) combined with a chemotherapy resulted in a 21% (4/19) response rate in advanced solid tumor patients harboring a TP53 mutation and in those without a TP53 mutation, a 12% (4/33) response rate was observed (PMID: 27601554). 27601554
TP53 mutant Advanced Solid Tumor predicted - sensitive Adavosertib Phase I Actionable In a Phase I trial, Adavosertib (MK-1775) treatment resulted in a prtial response in 3 and progressive disease in 2 of 6 patients with advanced solid tumors harboring TP53 mutations (J Clin Oncol 38: 2020 (suppl; abstr 3624); NCT01748825). detail...
TP53 mutant esophagus adenocarcinoma predicted - sensitive Adavosertib Preclinical - Cell line xenograft Actionable In a preclinical study, Adavosertib (MK-1775) treatment inhibited phosphorylation of Wee1 and Cdk1, and reduced viability of TP53-mutant esophageal adenocarcinoma cells in culture, and led to partial tumor growth delay in cell line xenograft models (PMID: 32220892). 32220892

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Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT02087241 Phase II Adavosertib Carboplatin + Pemetrexed Disodium Ph II Trial of Carboplatin and Pemetrexed With or Without AZD1775 for Untreated Lung Cancer Terminated USA 0
NCT03253679 Phase II Adavosertib WEE1 Inhibitor AZD1775 in Treating Patients With Advanced Refractory Solid Tumors With CCNE1 Amplification Suspended USA 0
NCT01922076 Phase I Adavosertib WEE1 Inhibitor MK-1775 and Local Radiation Therapy in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas Active, not recruiting USA | CAN 0
NCT02465060 Phase II Erdafitinib Copanlisib Trametinib Crizotinib Sunitinib Sapanisertib Nivolumab AZD4547 Dasatinib Pertuzumab + Trastuzumab Dabrafenib + Trametinib Binimetinib Adavosertib Osimertinib Palbociclib Afatinib Capivasertib Defactinib GSK2636771 Vismodegib Ado-trastuzumab emtansine Larotrectinib Taselisib Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) Recruiting USA 2
NCT04460937 Phase I Adavosertib Testing the Addition of an Anti-cancer Drug, Adavosertib, to Radiation Therapy for Patients With Incurable Esophageal and Gastroesophageal Junction Cancers Recruiting USA 0
NCT03333824 Phase I Adavosertib Effects of AZD1775 on the PK Substrates for CYP3A, CYP2C19, CYP1A2 and on QT Interval in Patients With Advanced Cancer Completed USA 0
NCT02659241 Phase I Adavosertib A Pilot Study of Induction Wee1 Inhibition in Ovarian Cancer Recruiting USA 0
NCT03284385 Phase II Adavosertib Testing AZD1775 in Advanced Solid Tumors That Have a Mutation Called SETD2 Recruiting USA 0
NCT02194829 Phase Ib/II Paclitaxel Gemcitabine Adavosertib Paclitaxel Albumin-Stabilized Nanoparticle Formulation and Gemcitabine Hydrochloride With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Previously Untreated Pancreatic Cancer That Is Metastatic or Cannot Be Removed by Surgery Active, not recruiting USA 0
NCT01357161 Phase II Carboplatin Adavosertib Paclitaxel A Study of MK-1775 in Combination With Paclitaxel and Carboplatin Versus Paclitaxel and Carboplatin Alone for Participants With Platinum-Sensitive Ovarian Tumors With the P53 Gene Mutation (MK-1775-004) Completed 0
NCT02341456 Phase I Adavosertib Carboplatin Paclitaxel Phase Ib Study AZD1775 in Combination With Carboplatin and Paclitaxel in Adult Asian Patients With Solid Tumours Completed 3
NCT02196168 Phase II Adavosertib Cisplatin Cisplatin With or Without WEE1 Inhibitor MK-1775 in Treating Patients With Recurrent or Metastatic Head and Neck Cancer Terminated CAN 0
NCT02666950 Phase II Adavosertib Cytarabine WEE1 Inhibitor AZD1775 With or Without Cytarabine in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome Completed USA 0
NCT04590248 Phase II Adavosertib A Study of Adavosertib as Treatment for Uterine Serous Carcinoma (ADAGIO) Recruiting USA | CAN 4
NCT04949425 Phase I Adavosertib A Study to Assess the Safety and Tolerability of Adavosertib for Patients With Advanced Solid Tumours Recruiting USA 2
NCT02511795 Phase I Adavosertib Olaparib AZD1775 Combined With Olaparib in Patients With Refractory Solid Tumors Completed USA | CAN 0
NCT03668340 Phase II Adavosertib AZD1775 in Women With Recurrent or Persistent Uterine Serous Carcinoma or Uterine Carcinosarcoma Recruiting USA 0
NCT02508246 Phase I Adavosertib Docetaxel Cisplatin AZD1775, Docetaxel, and Cisplatin Before Surgery in Treating Patients With Borderline Resectable Stage III-IVB Squamous Cell Carcinoma of the Head and Neck Completed USA 0
NCT03385655 Phase II Savolitinib Darolutamide Adavosertib Prostate Cancer Biomarker Enrichment and Treatment Selection Recruiting CAN 0
NCT02513563 Phase II Carboplatin + Paclitaxel Adavosertib AZD1775 Plus Carboplatin-Paclitaxel in Squamous Cell Lung Cancer Recruiting USA 0
NCT02087176 Phase II Adavosertib Pegfilgrastim A Placebo Controlled Study Comparing AZD1775+ Docetaxel Versus Placebo+Docetaxel to Treat Lung Cancer Terminated USA 0
NCT02610075 Phase I Adavosertib Study to Determine MTD of AZD1775 Monotherapy in Patients With Locally Advanced or Metastatic Solid Tumours. Completed USA 0
NCT01748825 Phase I Adavosertib MK-1775 for Advanced Solid Tumors Completed USA 0
NCT02791919 Phase I Adavosertib Cytarabine + Filgrastim + Fludarabine Wee1 Kinase Inhibitor AZD1775 and Combination Chemotherapy in Treating Children, Adolescents and Young Adults With Relapsed or Refractory Acute Myeloid Leukemia Withdrawn 0
NCT03313557 Phase I Adavosertib AZD1775 Continued Access Study to Assess Safety and Tolerability for Patients Enrolled in AZD1775 Clinical Pharmacology Studies Completed USA 3


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