Molecular Profile Detail

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Profile Name HRAS mutant
Gene Variant Detail

HRAS mutant (unknown)

Relevant Treatment Approaches

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Molecular Profile Indication/Tumor Type Response Type Relevant Treatment Approaches Therapy Name Approval Status Evidence Type Efficacy Evidence References
HRAS mutant salivary gland cancer predicted - sensitive Tipifarnib Phase II Actionable In a Phase II trial (KO-TIP-001), Zarnestra (tipifarnib) treatment resulted in an objective response rate of 8% (1/12) in patients with recurrent or metastatic salivary gland cancer harboring HRAS mutations, with a median progression-free survival of 7 months (J Clin Oncol 38: 2020 (suppl; abstr 6504); NCT02383927). detail...
HRAS mutant urinary bladder cancer sensitive Metformin Preclinical Actionable In a preclinical study, mouse models of bladder cancer harboring an HRAS mutation were sensitive to Glucophage (metformin), resulting in tumor growth reduction and prevention of hyperplasia regression (PMID: 26921394). 26921394
HRAS mutant head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Phase II Actionable In a Phase II trial (KO-TIP-001), Zarnestra (tipifarnib) treatment resulted in an objective response rate of 56% (10/18) in patients with head and neck squamous cell carcinoma harboring HRAS missense mutations at a variant allele frequency over 20%, with a median progression-free survival of 6.1 months (J Clin Oncol 38: 2020 (suppl; abstr 6504); NCT02383927). detail...
HRAS mutant Advanced Solid Tumor predicted - sensitive Selumetinib Preclinical - Cell culture Actionable In a preclinical study, human solid tumor cell lines harboring HRAS mutations demonstrated increased sensitivity to growth inhibition by Selumetinib (AZD6244) in culture compared to cell lines with wild-type HRAS (PMID: 26544513). 26544513
HRAS mutant Advanced Solid Tumor predicted - sensitive Binimetinib Preclinical - Cell culture Actionable In a preclinical study, Binimetinib (MEK162) inhibited growth and induced apoptosis in human solid tumor cell lines harboring HRAS mutations in culture (PMID: 26544513). 26544513
HRAS mutant ovarian cancer predicted - sensitive Alpelisib + Binimetinib Phase Ib/II Actionable In a Phase Ib study, Alpelisib (BYL719) in combination with Binimetinib (MEK162) demonstrated preliminary safety and efficacy in patients with RAS-mutant advanced solid tumors, including patients with ovarian cancer (J Clin Oncol 32:5s, 2014 (suppl; abstr 9051). detail...
HRAS mutant breast cancer decreased response PI-273 Preclinical - Cell culture Actionable In a preclinical study, breast cancer cell lines harboring RAS mutations, including HRAS-mutant cell lines, demonstrated decreased sensitivity to growth inhibition by PI-273, in culture (PMID: 28827373). 28827373
HRAS mutant Advanced Solid Tumor predicted - sensitive Everolimus Preclinical - Cell culture Actionable In a preclinical study, human solid tumor cell lines harboring HRAS mutations demonstrated increased sensitivity to growth inhibition by Afinitor (everolimus) in culture compared to cell lines with wild-type HRAS (PMID: 26544513). 26544513
HRAS mutant transitional cell carcinoma predicted - sensitive Tipifarnib Phase II Actionable In a Phase II trial (IST-01), Zarnestra (tipifarnib) treatment resulted in an objective response in 42% (5/12) of patients with urothelial carcinoma harboring HRAS mutations, with a median progression-free survival of 5.1 months (J Clin Oncol 38: 2020 (suppl; abstr 6504); NCT02535650). detail...
HRAS mutant salivary gland carcinoma sensitive Tipifarnib Clinical Study Actionable In a clinical study, Zarnestra (tipifarnib) treatment resulted in an overall response rate of 8% (n=13) with one ongoing partial response with a duration of 14 months and stable disease as the best response in 58% (7/12) of evaluable patients with HRAS-mutant metastatic salivary gland carcinoma, and a median overall survival of 18 months, and a median progression-free survival of 7 months (PMID: 32557577). 32557577
HRAS mutant thyroid gland medullary carcinoma sensitive Cabozantinib Phase III Actionable In a Phase III trial, Cometriq (cabozantinib) treatment resulted in improved progression free survival (47 vs 8 weeks) compared to placebo in thyroid medullary carcinoma patients harboring RAS mutations (PMID: 27525386). 27525386
HRAS mutant endometrial cancer sensitive Trametinib Preclinical Actionable In a preclinical study, Mekinist (trametinib) inhibited growth of human endometrial cancer cells harboring mutant HRAS in culture (PMID: 26343583). 26343583
HRAS mutant transitional cell carcinoma resistant Trametinib Preclinical Actionable In a preclinical study, human urinary transitional cell carcinoma cells harboring mutant HRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). 26343583
Clinical Trial Phase Therapies Title Recruitment Status
NCT02857270 Phase I LY3214996 Gemcitabine + LY3214996 + Nab-paclitaxel LY3214996 + Midazolam Abemaciclib + LY3214996 A Study of LY3214996 Administered Alone or in Combination With Other Agents in Participants With Advanced/Metastatic Cancer Recruiting
NCT02292758 Phase II Bevacizumab + Cetuximab + Irinotecan Cetuximab + Irinotecan Phase II Trial of Irinotecan, Cetuximab, and Bevacizumab Compared With Irinotecan, Cetuximab, and Placebo in KRAS-Wildtype, Irinotecan-Refractory, Metastatic Colorectal Cancer Completed
NCT03051035 Phase I KO-947 First-in-Human Study of KO-947 in Non-Hematological Malignancies Active, not recruiting
NCT04211337 Phase III Vandetanib Cabozantinib Selpercatinib A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531) Recruiting
NCT02383927 Phase II Tipifarnib Phase II Study of Tipifarnib in Squamous Head and Neck Cancer With HRAS Mutations Active, not recruiting
NCT01737502 Phase Ib/II Auranofin + Sirolimus Sirolimus and Auranofin in Treating Patients With Advanced or Recurrent Non-Small Cell Lung Cancer or Small Cell Lung Cancer Recruiting
NCT02022982 Phase Ib/II Palbociclib + PD-0325901 PALBOCICLIB + PD-0325901 for NSCLC & Solid Tumors Active, not recruiting
NCT02747537 Phase II Irinotecan + Sorafenib Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors With Sorafenib in Combination With Irinotecan Withdrawn
NCT03213691 Phase II Selumetinib Selumetinib Sulfate in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial) Suspended
NCT02224781 Phase III Ipilimumab + Nivolumab Dabrafenib + Trametinib Dabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma Recruiting
NCT02296242 Phase Ib/II Ulixertinib Phase 1/2 Study of the ERK1/2 Inhibitor BVD-523 in Patients With Acute Myelogenous Leukemia or Myelodysplastic Syndromes Completed
NCT01306045 Phase II Erlotinib Lapatinib MK2206 Sunitinib Selumetinib Molecular Profiling and Targeted Therapy for Advanced Non-Small Cell Lung Cancer, Small Cell Lung Cancer, and Thymic Malignancies Active, not recruiting
NCT03162627 Phase I Olaparib + Selumetinib Selumetinib and Olaparib in Solid Tumors Recruiting
NCT03913026 Phase II ECT-001 cord blood cells Mycophenolate mofetil Tacrolimus Cyclophosphamide + Fludarabine Cyclophosphamide + Fludarabine + Thiotepa UM171 Expanded Cord Blood In Patients With High-Risk Acute Leukemia/Myelodysplasia Recruiting
NCT03043313 Phase II Trastuzumab + Tucatinib Tucatinib Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer Recruiting
NCT01885195 Phase II Binimetinib MEK162 for Patients With RAS/RAF/MEK Activated Tumors Completed
NCT03317119 Phase I Trametinib + trifluridine/tipiracil hydrochloride Trametinib and TAS-102 in Treating Patients With Colon or Rectal Cancer That is Advanced, Metastatic, or Cannot Be Removed by Surgery Active, not recruiting
NCT03190915 Phase II Trametinib Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia Recruiting
NCT01449058 Phase Ib/II Alpelisib + Binimetinib A Phase Ib Study of MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors Completed
NCT03377361 Phase Ib/II Ipilimumab + Nivolumab Ipilimumab + Nivolumab + Trametinib An Investigational Immuno-therapy Study Of Nivolumab In Combination With Trametinib With Or Without Ipilimumab In Patients With Previously Treated Cancer of the Colon or Rectum That Has Spread Active, not recruiting
NCT04145297 Phase I Hydroxychloroquine + Ulixertinib Ulixertinib (BVD-523) and Hydroxychloroquine in Patients w Advanced MAPK-Mutated Gastrointestinal Adenocarcinomas (UTAH) Recruiting
NCT01907815 Phase II Trametinib + Uprosertib Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Acute Myeloid Leukemia Terminated
NCT03919292 Phase Ib/II Divalproex sodium + Neratinib Neratinib + Valproate in Advanced Solid Tumors, w/Expansion Cohort in Ras-Mutated Ca Recruiting
NCT03698994 Phase II Ulixertinib Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial) Recruiting
NCT03181100 Phase II Nab-paclitaxel Paclitaxel Atezolizumab + Cobimetinib Atezolizumab + Bevacizumab Atezolizumab + Nab-paclitaxel Atezolizumab + Cobimetinib + Vemurafenib Atezolizumab + Paclitaxel Atezolizumab Combinations With Chemotherapy for Anaplastic and Poorly Differentiated Thyroid Carcinomas Recruiting
NCT03415126 Phase I ASN007 A Study of ASN007 in Patients With Advanced Solid Tumors Completed