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, PMID: 32611648). |
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| Drug Name | Trade Name | Synonyms | Drug Classes | Drug Description |
|---|---|---|---|---|
| Adavosertib | MK-1775|AZD1775|AZ1775|MK1775 | WEE1 Inhibitor 8 | 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 |
|---|---|---|---|---|---|---|---|
| FBXW7 del | Advanced Solid Tumor | sensitive | Adavosertib | Preclinical - Cell culture | Actionable | In a preclinical study, a cell line with knockout of FBXW7 demonstrated increased sensitivity to Adavosertib (MK-1775) compared to cells with wild-type FBXW7 in culture (PMID: 38032106). | 38032106 |
| 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 | 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 | 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 | 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; NCT00648648). | 27601554 |
| 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 |
| NRAS mut TP53 mut | colorectal cancer | no benefit | Adavosertib | Phase II | Actionable | In a Phase II trial (FOCUS4-C), Adavosertib (AZD1775) treatment was well-tolerated and resulted in an advantage in progression-free survival (PFS, HR 0.40, p=0.0051) but not overall survival (0.92, p=0.93) compared to active monitoring in patients with metastatic colorectal cancer harboring both RAS and TP53 mutations, however, patients with NRAS mutations or KRAS non-G12/G13 mutations did not benefit from Adavosertib (AZD1775) treatment in subgroup PFS analysis (PMID: 34538072). | 34538072 |
| FBXW7 R465H | cervical cancer | sensitive | Adavosertib | Preclinical - Cell culture | Actionable | In a preclinical study, a cervical cancer cell line harboring FBXW7 R465H demonstrated increased sensitivity to Adavosertib (MK-1775) treatment compared to a cell line with wild-type FBXW7 in culture (PMID: 38032106). | 38032106 |
| 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 | 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... |
| 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 | 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 | 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 |
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| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| NCT01748825 | Phase I | Adavosertib | MK-1775 for Advanced Solid Tumors | Completed | USA | 0 |
| NCT02659241 | Phase I | Adavosertib | A Pilot Study of Induction Wee1 Inhibition in Ovarian Cancer | Active, not recruiting | 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 | Completed | USA | CAN | 0 |
| NCT04590248 | Phase II | Adavosertib | A Study of Adavosertib as Treatment for Uterine Serous Carcinoma (ADAGIO) | Completed | USA | ITA | FRA | ESP | CAN | 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 |
| NCT03253679 | Phase II | Adavosertib | WEE1 Inhibitor AZD1775 in Treating Patients With Advanced Refractory Solid Tumors With CCNE1 Amplification | Completed | USA | 0 |
| NCT04949425 | Phase I | Adavosertib | A Study to Assess the Safety and Tolerability of Adavosertib for Patients With Advanced Solid Tumours | Terminated | USA | GBR | 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 |
| 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 | |
| NCT02087176 | Phase II | Adavosertib Pegfilgrastim | A Placebo Controlled Study Comparing AZD1775+ Docetaxel Versus Placebo+Docetaxel to Treat Lung Cancer | Terminated | USA | 0 |
| NCT03313557 | Phase I | Adavosertib | AZD1775 Continued Access Study to Assess Safety and Tolerability for Patients Enrolled in AZD1775 Clinical Pharmacology Studies | Completed | USA | NLD | GBR | FRA | 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 | AUS | 2 |
| 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 |
| NCT03668340 | Phase II | Adavosertib | AZD1775 in Women With Recurrent or Persistent Uterine Serous Carcinoma or Uterine Carcinosarcoma | Active, not 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 | 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 |
| NCT02511795 | Phase I | Adavosertib Olaparib | AZD1775 Combined With Olaparib in Patients With Refractory Solid Tumors | Completed | USA | CAN | 0 |
| NCT02610075 | Phase I | Adavosertib | Study to Determine MTD of AZD1775 Monotherapy in Patients With Locally Advanced or Metastatic Solid Tumours. | Completed | USA | 0 |
| NCT02513563 | Phase II | Carboplatin + Paclitaxel Adavosertib | AZD1775 Plus Carboplatin-Paclitaxel in Squamous Cell Lung Cancer | Completed | USA | 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 | Active, not recruiting | USA | 0 |
| NCT03284385 | Phase II | Adavosertib | Testing AZD1775 in Advanced Solid Tumors That Have a Mutation Called SETD2 | Active, not recruiting | USA | 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 |
| NCT03385655 | Phase II | Savolitinib Darolutamide Adavosertib | Prostate Cancer Biomarker Enrichment and Treatment Selection | Active, not recruiting | CAN | 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 |
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