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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). |
Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
---|---|---|---|---|
Adavosertib | MK-1775|AZD1775|AZ1775 | WEE1 Inhibitor 4 | Adavosertib (MK-1775) is a small molecule inhibitor of the tyrosine kinase WEE1 with potential antineoplastic sensitizing activity (PMID: 22084170, PMID: 32611648). |
Molecular Profile | Indication/Tumor Type | Response Type | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
---|---|---|---|---|---|---|---|
Unknown unknown | glioblastoma | 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 |
ATRX del | hepatocellular carcinoma | sensitive | Adavosertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Adavosertib (MK-1775) treatment resulted in cell cycle arrest, DNA damage, and apoptosis in hepatocellular carcinoma cell lines with ATRX gene knocked out via CRISPR-Cas9 in culture, and inhibited tumor growth in cell line xenograft models (PMID: 31551363). | 31551363 |
ATRX R781* | malignant glioma | sensitive | Adavosertib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Adavosertib (MK-1775) inhibited growth of patient-derived glioma cells harboring ATRX R781* in culture (PMID: 31551363). | 31551363 |
Unknown unknown | brain glioma | not applicable | Adavosertib | Preclinical | Actionable | In a preclinical study, Adavosertib (MK-1775) in combination with radiation, reduced survival of cells derived from pediatric patients with high-grade gliomas (PMID: 24305702). | 24305702 |
Unknown unknown | Advanced Solid Tumor | not applicable | Adavosertib | Phase I | Actionable | In a Phase I trial, Adavosertib (MK-1775) treatment resulted in a partial response in 17% (6/35) and stable disease in 51.4% (18/35) of patients with advanced solid tumors, with a median duration of response of 5.2 months (J Clin Oncol 38: 2020 (suppl; abstr 3624); NCT01748825). | detail... |
Unknown unknown | Advanced Solid Tumor | not applicable | Adavosertib | Phase I | Actionable | In a Phase I trial, Adavosertib (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 |
Unknown unknown | Advanced Solid Tumor | not applicable | Adavosertib | Phase I | Actionable | In a Phase I trial, Adavosertib (MK-1775) treatment demonstrated safety and preliminary efficacy, resulted in an overall response rate of 3.4% (2/62), a disease control rate of 48.4% (30/62), and a median progression-free survival of 2.7 months in patients with advanced solid tumors (AACR Annual Meeting 2019, Abstract CT022). | 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 |
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 |
Unknown unknown | head and neck squamous cell carcinoma | not applicable | Adavosertib | Preclinical | Actionable | In a preclinical study, Adavosertib (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 | colorectal cancer | not applicable | Adavosertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Adavosertib (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 | lung non-small cell carcinoma | not applicable | Adavosertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Adavosertib (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 |
ATRX S458* | malignant glioma | sensitive | Adavosertib | Preclinical - Patient cell culture | Actionable | In a preclinical study, Adavosertib (MK-1775) inhibited growth of patient-derived glioma cells harboring ATRX S458* in culture (PMID: 31551363). | 31551363 |
PDGFRA D842V | gastrointestinal stromal tumor | sensitive | Adavosertib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Adavosertib (MK-1775) inhibited cell growth and induced cell cycle arrest in gastrointestinal stromal tumor cells harboring PDGFRA D842V in culture, and inhibited tumor growth and led to prolonged survival in cell line xenograft models (PMID: 33320833). | 33320833 |
Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
---|---|---|---|---|---|---|
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 |
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 |
NCT03668340 | Phase II | Adavosertib | AZD1775 in Women With Recurrent or Persistent Uterine Serous Carcinoma or Uterine Carcinosarcoma | Recruiting | USA | 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 | |
NCT03385655 | Phase II | Savolitinib Darolutamide Adavosertib | Prostate Cancer Biomarker Enrichment and Treatment Selection | Recruiting | CAN | 0 |
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 |
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 |
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 | |
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 |
NCT03313557 | Phase I | Adavosertib | AZD1775 Continued Access Study to Assess Safety and Tolerability for Patients Enrolled in AZD1775 Clinical Pharmacology Studies | Completed | USA | 3 |
NCT02087176 | Phase II | Adavosertib Pegfilgrastim | A Placebo Controlled Study Comparing AZD1775+ Docetaxel Versus Placebo+Docetaxel to Treat Lung Cancer | Terminated | USA | 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 |
NCT02610075 | Phase I | Adavosertib | Study to Determine MTD of AZD1775 Monotherapy in Patients With Locally Advanced or Metastatic Solid Tumours. | Completed | 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 |
NCT01748825 | Phase I | Adavosertib | MK-1775 for Advanced Solid Tumors | Completed | 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 |
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 | |
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 |
NCT02513563 | Phase II | Carboplatin + Paclitaxel Adavosertib | AZD1775 Plus Carboplatin-Paclitaxel in Squamous Cell Lung Cancer | Recruiting | USA | 0 |
NCT02511795 | Phase I | Adavosertib Olaparib | AZD1775 Combined With Olaparib in Patients With Refractory Solid Tumors | Completed | USA | CAN | 0 |
NCT03284385 | Phase II | Adavosertib | Testing AZD1775 in Advanced Solid Tumors That Have a Mutation Called SETD2 | Recruiting | USA | 0 |
NCT03253679 | Phase II | Adavosertib | WEE1 Inhibitor AZD1775 in Treating Patients With Advanced Refractory Solid Tumors With CCNE1 Amplification | Suspended | USA | 0 |
NCT02659241 | Phase I | Adavosertib | A Pilot Study of Induction Wee1 Inhibition in Ovarian Cancer | Recruiting | USA | 0 |