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 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 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 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 head and neck squamous cell carcinoma predicted - sensitive Tipifarnib Preclinical - Cell culture Actionable In a preclinical study, head and neck squamous cell carcinoma cell lines harboring an HRAS mutation were sensitive to treatment with Zarnestra (tipifarnib), demonstrating reduced cell growth and decreased phosphorylation of Erk and Mek, and inhibition of spheroid viability in culture (PMID: 32727882). 32727882
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 55% (11/20) in patients with head and neck squamous cell carcinoma harboring HRAS missense mutations at a variant allele frequency over 20%, with nine patients achieved stable disease and a median progression-free survival of 5.6 months (PMID: 33750196; NCT02383927). 33750196
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
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 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 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 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 transitional cell carcinoma predicted - sensitive Tipifarnib Phase II Actionable In a Phase II trial, Zarnestra (tipifarnib) demonstrated manageable toxicity profile, resulted in an objective response rate of 33.3% (5/15) in patients with transitional cell carcinoma harboring HRAS missense (Q61R, G12S, G13R) or frameshift (V29Cfs*19) mutations, progression-free survival was significantly improved in patients harboring HRAS mutations (5.1 vs 0.8 months, HR=0.262) compared to wild-type patients (PMID: 32636318; NCT02535650). 32636318
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
Clinical Trial Phase Therapies Title Recruitment Status Covered Countries Other Countries
NCT04425239 Phase II Fluorouracil + Irinotecan + Leucovorin + Panitumumab Intermittent or Continuous Panitumumab Plus FOLFIRI for RAS/B-RAF Wild-type Metastatic Colorectal Cancer (IMPROVE) Active, not recruiting 1
NCT04310176 Phase II Bevacizumab + Capecitabine + Oxaliplatin Bevacizumab + Capecitabine Bevacizumab + Fluorouracil + Leucovorin + Oxaliplatin Bevacizumab + Fluorouracil Bevacizumab + Fluorouracil + Valproic acid Bevacizumab + Capecitabine + Valproic acid Bevacizumab + Fluorouracil + Leucovorin + Oxaliplatin + Valproic acid Bevacizumab + Capecitabine + Oxaliplatin + Valproic acid Valproic Acid in Combination With Bevacizumab and Oxaliplatin/Fluoropyrimidine Regimens in Patients With Ras-mutated Metastatic Colorectal Cancer (REVOLUTION) Recruiting 1
NCT04892017 Phase I DCC-3116 DCC-3116 + Trametinib A Safety, Tolerability and PK Study of DCC-3116 in Patients With RAS or RAF Mutant Advanced or Metastatic Solid Tumors. Recruiting USA 0
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 USA 0
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 Active, not recruiting USA 0
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 USA 0
NCT03415126 Phase I ASN007 A Study of ASN007 in Patients With Advanced Solid Tumors Completed USA 0
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 CAN 0
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 USA 0
NCT03244956 Phase II Trametinib Dabrafenib + Trametinib Efficacy of MEK (Trametinib) and BRAFV600E (Dabrafenib) Inhibitors With Radioactive Iodine (RAI) for the Treatment of Refractory Metastatic Differentiated Thyroid Cancer (MERAIODE) Active, not recruiting 1
NCT02383927 Phase II Tipifarnib Phase II Study of Tipifarnib in Squamous Head and Neck Cancer With HRAS Mutations Completed USA 9
NCT03719690 Phase II Tipifarnib Safety and Efficacy of Tipifarnib in Head and Neck Cancer With HRAS Mutations and Impact of HRAS on Response to Therapy (AIM-HN/SEQ-HN) Recruiting USA 17
NCT04034173 Phase II Fluorouracil + Irinotecan + Leucovorin + Panitumumab Optimal Anti-EGFR Treatment of mCRC Patients With Low-Frequency RAS Mutation Not yet recruiting 1
NCT03919292 Phase Ib/II Divalproex sodium + Neratinib Neratinib + Valproate in Advanced Solid Tumors, w/Expansion Cohort in Ras-Mutated Ca Recruiting USA 0
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 Active, not recruiting USA 3
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) Active, not recruiting USA 1
NCT04072198 Phase II Bevacizumab + Fluorouracil + Irinotecan + Leucovorin + Nivolumab + Oxaliplatin Nivolumab Plus FOLFOXIRI/Bevacizumab in First Line Chemotherapy of Advanced Colorectal Cancer RASm/BRAFm Patients (NIVACOR) Recruiting 1
NCT01885195 Phase II Binimetinib MEK162 for Patients With RAS/RAF/MEK Activated Tumors Completed USA 0
NCT02747537 Phase II Irinotecan + Sorafenib Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors With Sorafenib in Combination With Irinotecan Withdrawn 0
NCT03714958 Phase I HDM201 + Trametinib Trametinib + HDM201 in CRC Patients With RAS/RAF Mutant and TP53 Wild-type Advanced/Metastatic Colorectal Cancer Mutant and TP53 Wild-type (TRAHD) Recruiting 1
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 USA 0
NCT04776655 Phase III Bevacizumab + Fluorouracil + Irinotecan + Leucovorin Cetuximab + Fluorouracil + Irinotecan + Leucovorin Study in mCRC Patients RAS/BRAF wt Tissue and RAS Mutated LIquid BIopsy to Compare FOLFIRI Plus CetuxiMAb or BevacizumaB (LIBImAb) Recruiting 1
NCT04511845 Phase I SPYK04 A Dose-Escalation Study of SPYK04 in Patients With Locally Advanced or Metastatic Solid Tumors (With Expansion). Recruiting USA 1
NCT03983993 Phase II Niraparib + Panitumumab Niraparib and Panitumumab in Patients With Advanced or Metastatic Colorectal Cancer (NIPAVect) Recruiting USA 0
NCT04211337 Phase III Vandetanib Cabozantinib Selpercatinib A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531) Recruiting USA | CAN 19
NCT03181100 Phase II Atezolizumab + Cobimetinib Atezolizumab + Bevacizumab Atezolizumab + Nab-paclitaxel Atezolizumab + Cobimetinib + Vemurafenib Atezolizumab + Paclitaxel Atezolizumab With Chemotherapy in Treating Patients With Anaplastic or Poorly Differentiated Thyroid Cancer Recruiting USA 0
NCT01907815 Phase II Trametinib + Uprosertib Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Acute Myeloid Leukemia Terminated USA 0
NCT03051035 Phase I KO-947 First-in-Human Study of KO-947 in Non-Hematological Malignancies Terminated USA 1
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) Active, not recruiting USA 1
NCT03190915 Phase II Trametinib Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia Recruiting USA 0
NCT03043313 Phase II Trastuzumab + Tucatinib Tucatinib Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer Active, not recruiting USA 4
NCT01449058 Phase Ib/II Alpelisib + Binimetinib A Phase Ib Study of MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors Completed USA 6
NCT03162627 Phase I Olaparib + Selumetinib Selumetinib and Olaparib in Solid Tumors Recruiting USA 0
NCT03496766 Phase II Tipifarnib Tipifarnib in Advanced Squamous NSCLC With Oncogen HRAS MutAtionS Recruiting 1
NCT04800822 Phase I PF-07284892 Cetuximab + Encorafenib + PF-07284892 Lorlatinib + PF-07284892 Binimetinib + PF-07284892 PF-07284892 in Participants With Advanced Solid Tumors Recruiting USA 0
NCT04854434 Phase II Trifluridine-tipiracil hydrochloride Pembrolizumab + Selinexor Selinexor A Study to Evaluate the Safety and Efficacy of Selinexor With or Without Pembrolizumab Versus Standard of Care in Previously Treated Metastatic Colorectal Cancer With RAS Mutations Recruiting USA 0
NCT04515394 Phase II Cetuximab + Tepotinib Study of Tepotinib Combined With Cetuximab in Participants Left-Sided Metastatic Colorectal Cancer (mCRC) Acquired Resistance Due to Mesenchymal Epithelial Transition (MET) Amplification Active, not recruiting USA 7
NCT04145297 Phase I Hydroxychloroquine + Ulixertinib Ulixertinib (BVD-523) and Hydroxychloroquine in Patients w Advanced MAPK-Mutated Gastrointestinal Adenocarcinomas (UTAH) Recruiting USA 0
NCT02022982 Phase Ib/II Palbociclib + PD-0325901 PALBOCICLIB + PD-0325901 for NSCLC & Solid Tumors Active, not recruiting USA 0
NCT03317119 Phase I Trametinib + Trifluridine-tipiracil hydrochloride Trametinib and Trifluridine and Tipiracil Hydrochloride in Treating Patients With Colon or Rectal Cancer That is Advanced, Metastatic, or Cannot Be Removed by Surgery Active, not recruiting USA 0
NCT04566393 Expanded access Ulixertinib Expanded Access to Ulixertinib (BVD-523) in Patients With Advanced MAPK Pathway-Altered Malignancies Available USA 0