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| Profile Name | HRAS mutant |
| Gene Variant Detail | |
| Relevant Treatment Approaches |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 | 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 |
| Clinical Trial | Phase | Therapies | Title | Recruitment Status | Covered Countries | Other Countries |
|---|---|---|---|---|---|---|
| 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 | Terminated | ||
| 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 | ||
| NCT04511845 | Phase I | SPYK04 | A Dose-Escalation Study of SPYK04 in Patients With Locally Advanced or Metastatic Solid Tumors (With Expansion). | 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 | ||
| 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) | Suspended | ||
| NCT03162627 | Phase I | Olaparib + Selumetinib | Selumetinib and Olaparib in Solid Tumors | Recruiting | ||
| 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 | ||
| NCT02747537 | Phase II | Irinotecan + Sorafenib | Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors With Sorafenib in Combination With Irinotecan | Withdrawn | ||
| NCT02383927 | Phase II | Tipifarnib | Phase II Study of Tipifarnib in Squamous Head and Neck Cancer With HRAS Mutations | Active, not recruiting | ||
| NCT02022982 | Phase Ib/II | Palbociclib + PD-0325901 | PALBOCICLIB + PD-0325901 for NSCLC & Solid Tumors | Active, not recruiting | ||
| NCT03415126 | Phase I | ASN007 | A Study of ASN007 in Patients With Advanced Solid Tumors | Completed | ||
| NCT04800822 | Phase I | PF-07284892 Cetuximab + Encorafenib + PF-07284892 Lorlatinib + PF-07284892 Binimetinib + PF-07284892 | PF-07284892 in Participants With Advanced Solid Tumors | Recruiting | ||
| NCT03043313 | Phase II | Trastuzumab + Tucatinib Tucatinib | Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer | Recruiting | ||
| 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 | ||
| NCT01907815 | Phase II | Trametinib + Uprosertib | Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Acute Myeloid Leukemia | Terminated | ||
| 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 | ||
| 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 | ||
| NCT01885195 | Phase II | Binimetinib | MEK162 for Patients With RAS/RAF/MEK Activated Tumors | Completed | ||
| NCT04211337 | Phase III | Vandetanib Cabozantinib Selpercatinib | A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531) | Recruiting | ||
| 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 | Recruiting | ||
| NCT03919292 | Phase Ib/II | Divalproex sodium + Neratinib | Neratinib + Valproate in Advanced Solid Tumors, w/Expansion Cohort in Ras-Mutated Ca | Recruiting | ||
| NCT01449058 | Phase Ib/II | Alpelisib + Binimetinib | A Phase Ib Study of MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors | Completed | ||
| 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 | ||
| NCT04145297 | Phase I | Hydroxychloroquine + Ulixertinib | Ulixertinib (BVD-523) and Hydroxychloroquine in Patients w Advanced MAPK-Mutated Gastrointestinal Adenocarcinomas (UTAH) | Recruiting | ||
| NCT03190915 | Phase II | Trametinib | Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia | Recruiting | ||
| 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 | ||
| 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 | ||
| NCT04566393 | Expanded access | Ulixertinib | Expanded Access to Ulixertinib (BVD-523) in Patients With Advanced MAPK Pathway-Altered Malignancies | Available | ||
| 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 | ||
| NCT03983993 | Phase II | Niraparib + Panitumumab | Niraparib and Panitumumab in Patients With Advanced or Metastatic Colorectal Cancer (NIPAVect) | Recruiting |