Therapy Detail

Therapy Name Adavosertib
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 WEE1 Inhibitor 2 Adavosertib (MK-1775) is a small molecule inhibitor of the tyrosine kinase WEE1 with potential antineoplastic sensitizing activity (PMID: 22084170).
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown non-small cell lung carcinoma not applicable Adavosertib Preclinical - Cell line xenograft Actionable In a preclinical study, MK-1775 inhibited cell proliferation and promoted DNA damage in human non-small cell lung carcinoma cell lines in culture, and promoted tumor regression in xenograft models (PMID: 23699655). 23699655
Unknown unknown brain glioma not applicable Adavosertib Preclinical Actionable In a preclinical study, MK-1175, in combination with radiation, reduced survival of cells derived from pediatric patients with high-grade gliomas (PMID: 24305702). 24305702
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 MK-1775 administration (PMID: 19887545). 19887545
KRAS mut STK11 inact mut non-small cell lung carcinoma predicted - sensitive Adavosertib Preclinical - Cell culture Actionable In a preclinical study, non-small cell lung carcinoma cell lines harboring KRAS mutations and STK11 inactivating mutations demonstrated increased sensitivity to MK-1775 compared to cells expressing wild-type STK11 in culture (PMID: 28652249). 28652249
TP53 mutant Advanced Solid Tumor sensitive Adavosertib Phase I Actionable In a retrospective analysis of a Phase I trial, 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 glioblastoma multiforme sensitive Adavosertib Preclinical - Pdx Actionable In a preclinical study, treatment with MK-1775 decreased CDK1 phosphorylation and reduced tumor growth in patient-derived xenograft models of glioblastoma multiforme that harbor TP53 mutations (PMID: 27196784). 27196784
Unknown unknown colorectal cancer not applicable Adavosertib Preclinical - Cell line xenograft Actionable In a preclinical study, MK-1775 inhibited cell proliferation and promoted DNA damage in a human colorectal cancer cell line in culture, and promoted tumor regression in xenograft models (PMID: 23699655). 23699655
Unknown unknown glioblastoma multiforme not applicable Adavosertib Phase 0 Actionable In a Phase 0 trial, Adavosertib (MK-1775) demonstrated safety and preliminary efficacy, resulted in good brain tumor penetration and Wee1 pathway inhibition in intraoperatively collected tumor samples from patients with first-recurrence glioblastoma (PMID: 29798906). 29798906
Unknown unknown head and neck squamous cell carcinoma not applicable Adavosertib Preclinical Actionable In a preclinical study, MK-1775 inhibited proliferation in various tumor cell lines, including head and neck squamous cell carcinoma cell lines, in culture (PMID: 23699655). 23699655
Unknown unknown Advanced Solid Tumor not applicable Adavosertib Phase I Actionable In a Phase I trial, MK-1775 combined with a chemotherapy resulted in a partial response of 10% (17/176) and stable disease in 53% (94/176) of patients with advanced solid tumors (PMID: 27601554). 27601554
NRAS mutant melanoma sensitive Adavosertib Preclinical Actionable In a preclinical study, MK-1775 showed efficacy in NRAS mutant melanoma and in mutant KRAS colorectal, pancreatic, and lung cancers (PMID: 24791855). 24791855
Clinical Trial Phase Therapies Title Recruitment Status
NCT03668340 Phase II Adavosertib A Phase 2 Study of the Wee1 Inhibitor AZD1775 in Women With Recurrent or Persistent Uterine Serous Carcinoma Recruiting
NCT02610075 Phase I Adavosertib Study to Determine MTD of AZD1775 Monotherapy in Patients With Locally Advanced or Metastatic Solid Tumours. Completed
NCT02087176 Phase II Adavosertib Pegfilgrastim A Placebo Controlled Study Comparing AZD1775+ Docetaxel Versus Placebo+Docetaxel to Treat Lung Cancer Terminated
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
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
NCT01922076 Phase I Adavosertib WEE1 Inhibitor MK-1775 and Local Radiation Therapy in Treating Younger Patients With Newly Diagnosed Diffuse Intrinsic Pontine Gliomas Recruiting
NCT03385655 Phase II Savolitinib ODM-201 Adavosertib Prostate Cancer Biomarker Enrichment and Treatment Selection Recruiting
NCT03333824 Phase I Adavosertib Effects of AZD1775 on the PK Substrates for CYP3A, CYP2C19, CYP1A2 and on QT Interval in Patients With Advanced Cancer Active, not recruiting
NCT02341456 Phase I Adavosertib Carboplatin Paclitaxel Phase Ib Study AZD1775 in Combination With Carboplatin and Paclitaxel in Adult Asian Patients With Solid Tumours Completed
NCT03313557 Phase I Adavosertib AZD1775 Continued Access Study to Assess Safety and Tolerability for Patients Enrolled in AZD1775 Clinical Pharmacology Studies Recruiting
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 Active, not recruiting
NCT02513563 Phase II Paclitaxel + Carboplatin Adavosertib AZD1775 Plus Carboplatin-Paclitaxel in Squamous Cell Lung Cancer Recruiting
NCT02087241 Phase II Adavosertib Carboplatin + Pemetrexed Ph II Trial of Carboplatin and Pemetrexed With or Without AZD1775 for Untreated Lung Cancer Terminated
NCT02465060 Phase II Dabrafenib Trametinib Crizotinib Sunitinib Sapanisertib Nivolumab AZD4547 Dasatinib Binimetinib Adavosertib Osimertinib Trastuzumab Palbociclib Afatinib Capivasertib Defactinib GSK2636771 Vismodegib trastuzumab emtansine Larotrectinib Pertuzumab Taselisib Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial) Recruiting
NCT03284385 Phase II Adavosertib Adavosertib in Treating Patients With SETD2-Deficient Locally Advanced or Metastatic Solid Tumors Recruiting
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
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
NCT01748825 Phase I Adavosertib MK-1775 for Advanced Solid Tumors Active, not recruiting
NCT03253679 Phase II Adavosertib WEE1 Inhibitor AZD1775 in Treating Patients With Advanced Refractory Solid Tumors With CCNE1 Amplification Recruiting
NCT02666950 Phase II Adavosertib Cytarabine WEE1 Inhibitor AZD1775 With or Without Cytarabine in Treating Patients With Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome Completed
NCT02511795 Phase I Adavosertib Olaparib AZD1775 Combined With Olaparib in Patients With Refractory Solid Tumors Recruiting
NCT02659241 Phase I Adavosertib A Pilot Study of Induction Wee1 Inhibition in Ovarian Cancer Recruiting