Therapy Detail

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Therapy Name Vandetanib
Synonyms
Therapy Description

Caprelsa (vandetanib) is a multi-tyrosine kinase inhibitor with activity against VEGFR, EGFR, RET, SRC, and ABL1 kinases, potentially resulting in decreased tumor growth (PMID: 25031937, PMID: 25490448). Caprelsa (vandetanib) is FDA approved for use in medullary thyroid cancer (FDA.gov).

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Drug Name Trade Name Synonyms Drug Classes Drug Description
Vandetanib Caprelsa ZD6474|AZD6474|AZD 6474 ABL1 Inhibitor 7 EGFR Inhibitor (Pan) 61 RET Inhibitor 52 SRC Inhibitor 31 VEGFR Inhibitor (Pan) 36 Caprelsa (vandetanib) is a multi-tyrosine kinase inhibitor with activity against VEGFR, EGFR, RET, SRC, and ABL1 kinases, potentially resulting in decreased tumor growth (PMID: 25031937, PMID: 25490448). Caprelsa (vandetanib) is FDA approved for use in medullary thyroid cancer (FDA.gov).

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Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET D378_G385delinsE thyroid gland medullary carcinoma predicted - sensitive Vandetanib Case Reports/Case Series Actionable In a clinical case study, Caprelsa (vandetanib) treatment resulted in an ongoing biochemical response for more than 6 months in a pediatric patient 16 years old with metastatic medullary thyroid carcinoma harboring RET D378_G385delinsE (PMID: 28209747). 28209747
RET S891A thyroid gland medullary carcinoma predicted - sensitive Vandetanib Case Reports/Case Series Actionable In a clinical case study, neoadjuvant Caprelsa (vandetanib) treatment resulted in a 65% decrease in the thyroid mass and cervical lymph nodes allowing for surgical resection in a pediatric patient with medullary thyroid carcinoma harboring RET S891A (PMID: 38207224). 38207224
RET wild-type lung small cell carcinoma sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited growth of small cell lung carcinoma lines expressing wild-type RET (PMID: 25122427). 25122427
ALK F1174L neuroblastoma sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) treatment resulted in decreased tumor weight in a Mycn-overexpressing neuroblastoma transgenic mouse model with ALK F1174L (corresponds to F1178L in mouse) and subsequent upregulation of Ret (PMID: 24811913). 24811913
RET D898_E901del thyroid gland medullary carcinoma predicted - resistant Vandetanib Case Reports/Case Series Actionable In a clinical case study, a patient with metastatic medullary thyroid carcinoma harboring RET D898_E901del demonstrated primary resistance to Caprelsa (vandetanib) treatment (PMID: 37535881). 37535881
RET fusion lung non-small cell carcinoma sensitive Vandetanib Phase II Actionable In a Phase II trial, Caprelsa (vandetanib) treatment resulted in a disease control rate of 88% (15/17), median progression-free survival (PFS) of 4.7 months, and partial response in 53% (9/17) of non-small cell lung adenocarcinoma patients harboring RET fusions (J Clin Oncol 34, 2016 (suppl; abstr 9012)). detail...
RET fusion lung non-small cell carcinoma sensitive Vandetanib Phase II Actionable In a Phase II trial, Caprelsa (vandetanib) treatment resulted in partial remission in 17% (3/18) and stable disease in 44% (8/18) of non-small cell lung adenocarcinoma patients harboring RET fusions (J Clin Oncol 34, 2016 (suppl; abstr 9013)). detail...
RET E768D Advanced Solid Tumor sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET E768D in culture (PMID: 15184865). 15184865
RET S891A Advanced Solid Tumor sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET S891A in culture (PMID: 15184865). 15184865
RET V804M Advanced Solid Tumor resistant Vandetanib Preclinical Actionable In a preclinical study, transformed cells expressing RET V804M demonstrated resistance to growth inhibition by Caprelsa (vandetanib) in culture (PMID: 15184865). 15184865
RET C634R RET Y806E Advanced Solid Tumor resistant Vandetanib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells co-expressing RET C634R and RET Y806E were resistant to treatment with Caprelsa (vandetanib) in culture (PMID: 19029224). 19029224
RET M918T Advanced Solid Tumor sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation and transforming activity in cells expressing RET M918T in culture (PMID: 15184865). 15184865
RET C634R RET V804M Advanced Solid Tumor resistant Vandetanib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells co-expressing RET C634R and RET V804M were resistant to treatment with Caprelsa (vandetanib) in culture (PMID: 19029224). 19029224
RET D898_E901del Advanced Solid Tumor predicted - sensitive Vandetanib Preclinical - Cell culture Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret phosphorylation and proliferation in a transformed cell line expressing RET D898_E901del, but to a lesser degree than cells expressing RET C634R in culture (PMID: 37535881). 37535881
RET V804L Advanced Solid Tumor resistant Vandetanib Preclinical Actionable In a preclinical study, transformed cells expressing RET V804L demonstrated resistance to growth inhibition by Caprelsa (vandetanib) in culture (PMID: 15184865). 15184865
RET C634R RET Y806C Advanced Solid Tumor resistant Vandetanib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells co-expressing RET C634R and RET Y806C were resistant to treatment with Caprelsa (vandetanib) in culture (PMID: 19029224). 19029224
RET C634R RET Y806F Advanced Solid Tumor predicted - sensitive Vandetanib Preclinical - Cell culture Actionable In a preclinical study, transformed human cells co-expressing RET C634R and RET Y806F in culture demonstrated inhibition of Ret phosphorylation and activity in kinase assays when treated with Caprelsa (vandetanib) (PMID: 19029224). 19029224
RET Y791F Advanced Solid Tumor sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET Y791F in culture (PMID: 15184865). 15184865
RET rearrange lung non-small cell carcinoma sensitive Vandetanib Phase II Actionable In a Phase II trial, treatment with Caprelsa (vandetanib) resulted in an objective response rate of 18% (3/17, all partial responses) and disease control rate of 65% (stable disease in 47% (8/17) + partial response in 18% (3/17)) and median progression-free survival of 4.5 months in patients with RET-rearranged metastatic or recurrent non-small cell lung cancer (PMID: 27803005; NCT01823068). 27803005
RET rearrange lung non-small cell carcinoma sensitive Vandetanib Clinical Study Actionable In a clinical study, analysis of patients with RET-rearranged non-small cell lung cancer treated with RET inhibitors demonstrated a response rate of 18% (2/11, all partial responses) and stable disease in 27% (3/11) of patients following Caprelsa (vandetanib) treatment (PMID: 28447912). 28447912
ALK R1275Q neuroblastoma sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) treatment resulted in decreased tumor weight in a Mycn-overexpressing neuroblastoma transgenic mouse model with ALK R1275Q (corresponds to R1279Q in mouse) and subsequent upregulation of Ret (PMID: 24811913). 24811913
RET M918T lung small cell carcinoma sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited growth of small cell lung carcinoma lines expressing RET M918T (PMID: 25122427). 25122427
RET L790F Advanced Solid Tumor sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET L790F in culture (PMID: 15184865). 15184865
APC inact mut colon cancer sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) reduced the number of dextran sodium sulfate-induced tumors in an APC-deficient mouse model for colon cancer (PMID: 20811697). 20811697
RET C634R RET V804G Advanced Solid Tumor sensitive Vandetanib Preclinical Actionable In a preclinical study, transformed cell lines expressing Ret protein carrying both C634R and V804G mutations were more sensitive to Vandetanib induced inhibition of Ret activity than cells expressing Ret C634R alone in culture (PMID: 15184865). 15184865
RET A883F Advanced Solid Tumor sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret autophosphorylation in transformed cells expressing RET A883F in culture (PMID: 15184865). 15184865
RET L633_A639del thyroid gland medullary carcinoma predicted - sensitive Vandetanib Case Reports/Case Series Actionable In a clinical case study, Caprelsa (vandetanib) treatment resulted in disease stabilization in a patient with metastatic medullary thyroid carcinoma harboring RET L633_A639del (PMID: 28209747). 28209747
RET C634R Advanced Solid Tumor sensitive Vandetanib Preclinical - Cell culture Actionable In a preclinical study, Caprelsa (vandetanib) inhibited Ret phosphorylation and proliferation in a transformed cell line expressing RET C634R in culture (PMID: 37535881). 37535881
RET C634R Advanced Solid Tumor sensitive Vandetanib Preclinical Actionable In a preclinical study, Caprelsa (vandetanib) inhibited RET phosphorylation and decreased growth of transformed cells expressing RET C634R in culture (PMID: 15184865). 15184865

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Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT01414426 Phase II Vandetanib Vandetanib in Preventing Head and Neck Cancer in Patients With Precancerous Head and Neck Lesions Completed USA 0
NCT01934335 Phase I Vandetanib Effect of Vandetanib on Cellular Markers in Invasive Breast Cancer Terminated USA 0
NCT01876784 Phase III Vandetanib Evaluation of Efficacy, Safety of Vandetanib in Patients With Differentiated Thyroid Cancer Completed USA | ITA | FRA | ESP 8
NCT00566995 Phase II Vandetanib Phase II Study of Vandetanib in Individuals With Kidney Cancer Completed USA 0
NCT01585415 Phase I Vandetanib Vemurafenib and White Blood Cell Therapy for Advanced Melanoma Terminated USA 0
NCT02015065 Phase II Vandetanib Phase II Trial of Vandetanib in Children and Adults With Wild-Type Gastrointestinal Stromal Tumors Completed USA 0
NCT04211337 Phase III Vandetanib Cabozantinib Selpercatinib A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531) Active, not recruiting USA | ITA | GBR | FRA | ESP | DEU | CAN | BEL | AUS 12
NCT02788201 Phase II Erlotinib Thiotepa Imatinib Dacarbazine Arsenic trioxide Idarubicin Mitomycin C Thioguanine Mercaptopurine Methotrexate Cladribine Epirubicin Gemcitabine Doxorubicin Bleomycin Etoposide Gefitinib Daunorubicin Lomustine Sorafenib Sunitinib Ifosfamide Asparaginase Ixabepilone Abiraterone Azacitidine Ruxolitinib Decitabine Axitinib Estramustine Floxuridine Lapatinib Carmustine Fludarabine Nilotinib Cisplatin Vismodegib Vandetanib Melphalan Busulfan Carboplatin Toremifene Crizotinib Dactinomycin Temsirolimus Vorinostat Romidepsin Fluorouracil Irinotecan Bortezomib Tamoxifen Topotecan Chlorambucil Pentostatin Eribulin Carfilzomib Vemurafenib Hydroxyurea Exemestane Vincristine Sulfate Dasatinib Mitoxantrone Vinblastine Cytarabine Tretinoin Clofarabine Teniposide Docetaxel Pazopanib Oxaliplatin Streptozocin Paclitaxel Bendamustine Mechlorethamine Mitotane Genomic Based Assignment of Therapy in Advanced Urothelial Carcinoma Completed USA 0
NCT04760288 Phase III Cabozantinib Pralsetinib Vandetanib A Study of Pralsetinib Versus Standard of Care (SOC) for Treatment of RET-Mutated Medullary Thyroid Cancer (MTC). (AcceleRET-MTC) Withdrawn ESP 0


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