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| Profile Name | NRAS 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 |
|---|---|---|---|---|---|---|---|---|
| NRAS mutant | biliary tract cancer | predicted - sensitive | Binimetinib | Phase I | Actionable | In a Phase I trial, Binimetinib (MEK162) treatment resulted in partial response in a biliary tract cancer patient harboring NRAS mutation (PMID: 28152546) | 28152546 | |
| NRAS mutant | melanoma | sensitive | S63845 + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, combination of S63845 and Mekinist (trametinib) resulted in potent cytotoxic effects in NRAS-mutated melanoma cells in culture compared to the cytostatic effect of Mekinist (trametinib) alone (PMID: 27760111). | 27760111 | |
| NRAS mutant | acute myeloid leukemia | predicted - resistant | Pazopanib | Preclinical - Patient cell culture | Actionable | In a preclinical study, NRAS mutations correlated with resistance to Votrient (pazopanib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). | 30333627 | |
| NRAS mutant | melanoma | conflicting | Palbociclib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cell lines were sensitive to treatment with Ibrance (palbociclib) in culture, demonstrating decreased cell viability, colony formation, and pathway activity, and increased cell cycle arrest (PMID: 30819666). | 30819666 | |
| NRAS mutant | melanoma | conflicting | Palbociclib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Ibrance (palbociclib) treatment resulted in stable tumor growth in melanoma cell line xenograft models harboring an NRAS mutation, however, growth later ensued and thus, demonstrated a lack of benefit (PMID: 27488531). | 27488531 | |
| NRAS mutant | leukemia | sensitive | Belvarafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Belvarafenib (HM95573) inhibited growth of NRAS mutant leukemia cells in culture (Cancer Res 2015;75(15 Suppl):Abstract nr 2607). | detail... | |
| NRAS mutant | acute myeloid leukemia | predicted - resistant | Vemurafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, NRAS mutations correlated with resistance to Zelboraf (vemurafenib) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). | 30333627 | |
| NRAS mutant | autonomic nervous system neoplasm | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human autonomic ganglia cancer cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 | |
| NRAS mutant | Advanced Solid Tumor | no benefit | LY3009120 | Case Reports/Case Series | Actionable | In a Phase I trial, LY3009120 did not achieve expected pharmacodynamic effects, resulted in stable disease as best overall response in 1 of 5 patients with advanced or metastatic cancer harboring NRAS mutations (PMID: 31645440; NCT02014116). | 31645440 | |
| NRAS mutant | melanoma | conflicting | Binimetinib | Phase II | Actionable | In a Phase II trial, Binimetinib (MEK162) treatment resulted in partial response in 20% (6/30), and stable disease in 43% (13/30) of melanoma patients harboring NRAS mutations, including Q61L (1/30), Q61K (9/30), and Q61R (15/30) (PMID: 23414587). | 23414587 | |
| NRAS mutant | melanoma | conflicting | Binimetinib | Phase III | Actionable | In a Phase III clinical trial, treatment with Binimetinib (MEK162) improved median progression-free survival compared to treatment with Deticene (dacarbazine) (2.8 mo. vs. 1.5 mo.), but did not improve overall survival in patients with NRAS-mutant melanoma (PMID: 28284557). | 28284557 | |
| NRAS mutant | central nervous system cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human central nervous system cancer cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 | |
| NRAS mutant | leukemia | sensitive | Alpelisib + Binimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination therapy of Alpelisib (BYL719) and Binimetinib (MEK162) led to a synergistic effect in leukemia cells harboring mutant NRAS, demonstrating cell death in culture (PMID: 29437705). | 29437705 | |
| NRAS mutant | colorectal cancer | no benefit | Cetuximab + Fluorouracil + Irinotecan + Leucovorin | Phase III | Actionable | In a retrospective analysis of a Phase III trial, the combination of Erbitux (cetuximab) and FOLFIRI did not demonstrate an improved clinical benefit compared to FOLFIRI alone in colorectal cancer patients with RAS mutations (PMID: 25605843). | 25605843 | |
| NRAS mutant | stomach carcinoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant gastric carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| NRAS mutant | thyroid gland cancer | sensitive | Selumetinib | Phase I | Actionable | In a Phase I study, selumetinib demonstrated an increase in iodine uptake and retention in a subgroup of patients with thyroid cancer that was refractory to radioiodine; including patients with BRAF and NRAS mutations disease (PMID: 23406027). | 23406027 | |
| NRAS mutant | melanoma | predicted - sensitive | Pembrolizumab | Clinical Study - Cohort | Actionable | In a clinical study, NRAS mutations were associated with higher 6-month objective response rate (53.3% vs. 19.6% without NRAS mutations; p=0.019) following treatment with Keytruda (pembrolizumab) or Opdivo (nivolumab) in patients with metastatic melanoma, however, progression-free survival and overall survival were similar between patients with and without NRAS mutations (PMID: 29973670). | 29973670 | |
| NRAS mutant | skin melanoma | sensitive | Binimetinib | Phase III | Actionable | In a Phase III trial, Binimetinib (MEK162) treatment resulted in improved progression free survival (2.8 months), objective response rate (15%, 40/269) and disease control rate (58%, 156/269) compared to Deticene (dacarbazine) (1.5 months, 7%, 25%, respectively) in NRAS-mutant cutaneous melanoma patients (J Clin Oncol 34, 2016 (suppl; abstr 9500)). | detail... | |
| NRAS mutant | skin melanoma | sensitive | Binimetinib | Guideline | Actionable | Mektovi (binimetinib) is included in guidelines as second-line therapy for patients with metastatic or unresectable cutaneous melanoma harboring an NRAS mutation (NCCN.org). | detail... | |
| NRAS mutant | multiple myeloma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human multiple myeloma cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 | |
| NRAS mutant | melanoma | predicted - sensitive | Palbociclib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, melanoma cell lines harboring an NRAS mutation were sensitive to the combination therapy of Ibrance (palbociclib) and Mekinist (trametinib) in culture, demonstrating reduced cell viability, colony formation, and pathway activity, and increased cell cycle arrest (PMID: 30819666). | 30819666 | |
| NRAS mutant | melanoma | sensitive | SBI-0640756 | Preclinical | Actionable | In a preclinical study, SBI-0640756 inhibited proliferation and transformation of human melanoma cell lines harboring NRAS mutation in culture (PMID: 26603897). | 26603897 | |
| NRAS mutant | colon cancer | resistant | GDC0879 | Preclinical - Cell culture | Actionable | In a preclinical study, colon cancer cells harboring NRAS mutations were resistant to GDC0879 induced growth inhibition in culture (PMID: 19276360). | 19276360 | |
| NRAS mutant | melanoma | sensitive | LY3009120 | Preclinical | Actionable | In a preclinical study, LY3009120 inhibited growth of NRAS mutant human melanoma cell lines in culture (PMID: 26343583). | 26343583 | |
| NRAS mutant | melanoma | sensitive | Binimetinib + Buparlisib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Binimetinib (MEK162) and Buparlisib (BKM120) resulted in improved cell growth inhibition compared to either agent alone in a metastatic melanoma cell line harboring an NRAS mutation (PMID: 27307593). | 27307593 | |
| NRAS mutant | acute myeloid leukemia | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human acute myeloid leukemia cell lines harboring mutant NRAS in culture (PMID: 26343583). | 26343583 | |
| NRAS mutant | transitional cell carcinoma | decreased response | Trametinib | Preclinical | Actionable | In a preclinical study, human urinary tract transitional cell carcinoma cells harboring mutant NRAS were moderately sensitive to Mekinist (trametinib) growth inhibition in culture (PMID: 26343583). | 26343583 | |
| NRAS mutant | Advanced Solid Tumor | predicted - sensitive | BGB-283 | Phase I | Actionable | In a Phase I trial, BGB-283 demonstrated safety and preliminary efficacy, resulted in partial response in 14% (4/29), and prolonged stable disease in 48% (14/29) of advanced solid tumor patients harboring mutations in KRAS, NRAS, and/or BRAF (AACR Annual Meeting, Apr 2016, abstract # CT005). | detail... | |
| NRAS mutant | melanoma | predicted - sensitive | Nivolumab | Clinical Study - Cohort | Actionable | In a clinical study, NRAS mutations were associated with higher 6-month objective response rate (53.3% vs. 19.6% without NRAS mutations; p=0.019) following treatment with Keytruda (pembrolizumab) or Opdivo (nivolumab) in patients with metastatic melanoma, however, progression-free survival and overall survival were similar between patients with and without NRAS mutations (PMID: 29973670). | 29973670 | |
| NRAS mutant | pancreatic cancer | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant pancreatic cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| NRAS mutant | neuroblastoma | sensitive | Alpelisib + Binimetinib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination therapy of Alpelisib (BYL719) and Binimetinib (MEK162) led to a synergistic effect in neuroblastoma cells harboring mutant NRAS, demonstrating cell death in culture (PMID: 29437705). | 29437705 | |
| NRAS mutant | melanoma | sensitive | Palbociclib + PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, the combination treatment of PD-0325901 and Ibrance (palbociclib) resulted in tumor regression in 33% (2/6) of melanoma xenograft models harboring an NRAS mutation (PMID: 27488531). | 27488531 | |
| NRAS mutant | melanoma | sensitive | BI-69A11 | Preclinical | Actionable | In a preclinical study, BI-69A11 inhibited proliferation and transformation of human melanoma cell lines harboring NRAS mutation in culture (PMID: 26603897). | 26603897 | |
| NRAS mutant | lung adenocarcinoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, human lung adenocarcinoma cell lines harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 | |
| NRAS mutant | melanoma | no benefit | PD-0325901 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PD-0325901 treatment resulted in stable tumor growth in melanoma cell line xenograft models harboring an NRAS mutation, however, growth later ensued and thus, demonstrates a lack of benefit (PMID: 27488531). | 27488531 | |
| NRAS mutant | melanoma | predicted - sensitive | Belvarafenib | Case Reports/Case Series | Actionable | In a Phase I trial, Belvarafenib (HM95573) treatment resulted in an unconfirmed partial response in a patient with NRAS mutant melanoma (Journal of Clinical Oncology 34, no. 15_suppl (May 20 2016) 2570-2570; NCT02405065). | detail... | |
| NRAS mutant | melanoma | predicted - sensitive | Belvarafenib | Phase I | Actionable | In Phase I trials, Belvarafenib (HM95573) treatment resulted in partial response in 44% (4/9) of patients with NRAS-mutant melanoma in a dose escalation study, and partial response in 22% (2/9) of NRAS-mutant melanoma patients in a dose expansion study (J Clin Oncol 37, 2019 (suppl; abstr 3000); NCT02405065, NCT03118817). | detail... | |
| NRAS mutant | Advanced Solid Tumor | sensitive | Obatoclax | Preclinical | Actionable | In a preclinical study, obatoclax decreased proliferation in human tumor cell lines with NRAS mutation in culture (PMID: 22460902). | 22460902 | |
| NRAS mutant | hematologic cancer | predicted - resistant | SHP099 | Preclinical | Actionable | In a preclinical study, hematopoietic cancer cell lines harboring NRAS mutations demonstrated resistance to SHP099 in cell culture (PMID: 27362227). | 27362227 | |
| NRAS mutant | Advanced Solid Tumor | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 resulted in tumor regression in patient derived xenograft (PDX) models harboring either a BRAF mutation, NRAS mutation, or KRAS mutation (EJC Dec 2016, 69:1; S126). | detail... | |
| NRAS mutant | Advanced Solid Tumor | no benefit | NS1 | Preclinical - Cell culture | Actionable | In a preclinical study, transformed cells expressing an NRAS mutation did not respond to treatment with NS1 in culture, resulting in sustained downstream signaling and cell transformation (PMID: 27820802). | 27820802 | |
| NRAS mutant | melanoma | sensitive | Tubastatin A | Preclinical | Actionable | In a preclinical study, Tubastatin A inhibited proliferation of NRAS mutant melanoma cell lines in culture (PMID: 25957812). | 25957812 | |
| NRAS mutant | cervix carcinoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant cervical carcinoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| NRAS mutant | melanoma | sensitive | CCT241161 | Preclinical | Actionable | In a preclinical study, CCT241161 inhibited growth of melanoma cells harboring NRAS mutations in culture (PMID: 25500121). | 25500121 | |
| NRAS mutant | Advanced Solid Tumor | no benefit | CC-90003 | Phase I | Actionable | In a Phase Ia trial, CC-90003 treatment did not result in any objective responses and demonstrated toxicity in advanced solid tumor patients harboring KRAS, NRAS, or BRAF mutations (J Clin Oncol 35, 2017 (suppl; abstr 2577)). | detail... | |
| NRAS mutant | melanoma | sensitive | SBI-0640726 | Preclinical | Actionable | In a preclinical study, SBI-0640726 inhibited proliferation and transformation of human melanoma cell lines harboring NRAS mutation in culture (PMID: 26603897). | 26603897 | |
| NRAS mutant | melanoma | sensitive | Buparlisib | Preclinical - Cell line xenograft | Actionable | In a preclinical study, Buparlisib (BKM120) treatment in human melanoma cell line xenograft models with brain metastases and harboring an NRAS mutation resulted in inhibition of brain tumor growth and an improved survival benefit (PMID: 27307593). | 27307593 | |
| NRAS mutant | melanoma | predicted - sensitive | Cobimetinib + UNC2025 | Preclinical - Cell culture | Actionable | In a preclinical study, the combination therapy of UNC2025 and Cotellic (cobimetinib) resulted in greater inhibition of colony formation and apoptotic induction in melanoma cells harboring an NRAS mutation in culture when compared to either therapy alone (PMID: 30482852). | 30482852 | |
| NRAS mutant | melanoma | sensitive | Trametinib | Phase I | Actionable | In a Phase I trial, Mekinist (trametinib) treatment resulted in stable disease in 29% (2/7) of patients with NRAS mutated melanoma (PMID: 22805292; NCT00687622). | 22805292 | |
| NRAS mutant | melanoma | sensitive | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, NRAS-mutant melanoma cell lines were sensitive to treatment with Mekinist (trametinib) in culture, demonstrating decreased cell viability, colony formation, and pathway activity, and increased cell cycle arrest (PMID: 30819666). | 30819666 | |
| NRAS mutant | hepatocellular carcinoma | sensitive | Refametinib + Sorafenib | Phase II | Actionable | In a Phase II trial, Refametinib (BAY86-9766) and Nexavar (sorafenib) combination treatment resulted in an objective response rate of 6.3% (1/16), a disease control rate of 43.8% (7/16), an overall survival of 12.7 months, and a progression-free survival of 1.5 months in patients unresectable or metastatic hepatocellular carcinoma harboring RAS (NRAS and KRAS) mutations (PMID: 29950351; NCT01915602). | 29950351 | |
| NRAS mutant | acute myeloid leukemia | predicted - sensitive | AZD5153 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, AZD5153 inhibited proliferation of acute myeloid leukemia cells harboring NRAS mutation in culture, resulted in tumor growth inhibition in cell line xenograft models (PMID: 27573426). | 27573426 | |
| NRAS mutant | colorectal cancer | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant colorectal cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| NRAS mutant | lymphoma | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of human lymphoma cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 | |
| NRAS mutant | non-Hodgkin lymphoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, human non-Hodgkin lymphoma cells harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 | |
| NRAS mutant | colorectal cancer | predicted - resistant | SYM004 | Preclinical - Pdx | Actionable | In a preclinical study, patient-derived xenograft (PDX) models of colorectal cancer harboring KRAS, NRAS or BRAF mutations demonstrated poor response to SYM004 treatment compared to wild-type models (PMID: 29423521). | 29423521 | |
| NRAS mutant | melanoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant melanoma (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | detail... | |
| NRAS mutant | ovarian cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of ovarian cancer cells harboring mutant NRAS in culture (PMID: 26343583). | 26343583 | |
| NRAS mutant | melanoma | resistant | Vemurafenib | Preclinical | Actionable | In a preclinical study, human melanoma cell lines harboring a mutation in NRAS were resistant to Zelboraf (vemurafenib) mediated growth inhibition in culture (PMID: 26343583). | 26343583 | |
| NRAS mutant | lung non-small cell carcinoma | predicted - sensitive | KO-947 | Preclinical - Pdx | Actionable | In a preclinical study, KO-947 inhibited Erk signaling and induced tumor regression in patient-derived xenograft models of NRAS-mutant non-small cell lung cancer (Cancer Res 2017;77(13 Suppl):Abstract nr 5168). | 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 | |
| NRAS mutant | liver cancer | sensitive | Trametinib | Preclinical | Actionable | In a preclinical study, Mekinist (trametinib) inhibited growth of liver cancer cell lines harboring mutant NRAS in culture (PMID: 26343583). | 26343583 | |
| NRAS mutant | sarcoma | resistant | Trametinib | Preclinical | Actionable | In a preclinical study, human sarcoma cells harboring mutant NRAS were insensitive to Mekinist (trametinib) in culture (PMID: 26343583). | 26343583 | |
| NRAS mutant | leukemia | predicted - sensitive | Trametinib | Phase Ib/II | Actionable | In a Phase Ib/II clinical trial, treatment with Mekinist (trametinib) resulted in an overall response rate of 28% in RAS-mutant leukemia patients, with 12% (7/57) of patients achieving complete remission (ASH 2015 Annual Meeting, Abst 677). | detail... | |
| NRAS mutant | acute myeloid leukemia | predicted - resistant | Tivozanib | Preclinical - Patient cell culture | Actionable | In a preclinical study, NRAS mutations correlated with resistance to Tivozanib (AV-951) in patient-derived acute myeloid leukemia samples in an ex vivo assay (PMID: 30333627). | 30333627 | |
| NRAS mutant | melanoma | predicted - sensitive | Ulixertinib | Phase I | Actionable | In a Phase I trial, treatment with BVD-523 (ulixertinib) resulted in a best response of stable disease in six melanoma patients and a partial response in three melanoma patients all harboring an NRAS mutation (PMID: 29247021). | 29247021 | |
| NRAS mutant | melanoma | sensitive | CCT196969 | Preclinical | Actionable | In a preclinical study, CCT196969 inhibited growth of melanoma cells harboring NRAS mutations in culture (PMID: 25500121). | 25500121 | |
| NRAS mutant | acute myeloid leukemia | sensitive | LY3009120 | Preclinical | Actionable | In a preclinical study, LY3009120 inhibited proliferation of human NRAS mutant acute myeloid leukemia cell lines in culture (PMID: 26343583). | 26343583 | |
| NRAS mutant | colorectal cancer | no benefit | Regorafenib | Phase II | Actionable | In a Phase II clinical trial (PREVIUM), Stivarga (regorafenib) treatment resulted in 0% (0/15) 6-month progression free survival (PFS), a 2.2-month median PFS, and a median overall survival of 3.3 months in metastatic colorectal cancer patients with KRAS (n=9), NRAS (n=3) or BRAF (n=2) mutations who failed first line therapy; however, the trial was terminated early due to poor accrual (PMID: 30120161; NCT02175654). | 30120161 | |
| NRAS mutant | Advanced Solid Tumor | sensitive | RAF709 | Preclinical - Cell culture | Actionable | In a preclinical study, cancer cell lines harboring NRAS mutations demonstrated increased sensitivity to RAF709 compared to NRAS wild-type cells in culture (PMID: 29343524). | 29343524 | |
| NRAS mutant | melanoma | sensitive | Binimetinib + Ribociclib | Phase Ib/II | Actionable | In a Phase Ib/II trial, the combination of Binimetinib (MEK162) and Kisqali (ribociclib) resulted in a partial response in 43% (6/14) and stable disease in 43% (6/14) of NRAS mutant melanoma patients (J Clin Oncol 32:5s, 2014 (Suppl;abstr 9009)). | detail... | |
| NRAS mutant | melanoma | sensitive | Binimetinib + Ribociclib | Phase Ib/II | Actionable | In a Phase Ib trial, the combination of Binimetinib (MEK162) and Kisqali (ribociclib) resulted in a median progression-free survival of 6.7 months, a partial response in 25% (4/16), and stable disease in 44% (7/16) of NRAS mutant melanoma patients (J Clin Oncol 35, 2017 (suppl; abstr 9519)). | detail... |
| Clinical Trial | Phase | Therapies | Title | Recruitment Status |
|---|---|---|---|---|
| NCT01781429 | Phase Ib/II | Ulixertinib | Phase I Dose-Escalation, Safety, Pharmacokinetic and Pharmacodynamic Study of BVD-523 in Patients With Advanced Malignancies | Completed |
| NCT03415126 | Phase I | ASN007 | A Study of ASN007 in Patients With Advanced Solid Tumors | Completed |
| NCT04145297 | Phase I | Hydroxychloroquine + Ulixertinib | Ulixertinib (BVD-523) and Hydroxychloroquine in Patients w Advanced MAPK-Mutated Gastrointestinal Adenocarcinomas (UTAH) | Recruiting |
| NCT02723006 | Phase I | MLN2480 + Nivolumab MLN1202 + Nivolumab Ipilimumab + Nivolumab + Vedolizumab | Study to Evaluate the Safety, Tolerability, and Pharmacodynamics of Investigational Treatments in Combination With Standard of Care Immune Checkpoint Inhibitors in Participants With Advanced Melanoma | Terminated |
| NCT03190915 | Phase II | Trametinib | Trametinib in Treating Patients With Relapsed or Refractory Juvenile Myelomonocytic Leukemia | Recruiting |
| NCT01915602 | Phase II | Refametinib + Sorafenib | Refametinib in Combination With Sorafenib in RAS Mutant Hepatocellular Carcinoma (HCC) | Completed |
| NCT04109456 | Phase I | BI 853520 + Cobimetinib BI 853520 | IN10018 Monotherapy and Combination Therapy for Metastatic Melanoma | Recruiting |
| 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 |
| NCT02089230 | Phase Ib/II | Binimetinib | MEK Inhibitor 162 Relapsed and/or Refractory Acute Myeloid Leukemia (AML) and Poor Prognosis, Not Suitable for or Unwilling to Receive Standard Therapy | Completed |
| 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 |
| 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 |
| 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 |
| NCT02610361 | Phase I | BGB-283 | Study of the Safety and Pharmacokinetics of BGB-283 in Patients With Solid Tumors | Completed |
| 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 |
| NCT01693068 | Phase II | Dacarbazine Pimasertib | Phase II Trial of Pimasertib Versus Dacarbazine in N-Ras Mutated Cutaneous Melanoma | Completed |
| NCT03919292 | Phase Ib/II | Divalproex sodium + Neratinib | Neratinib + Valproate in Advanced Solid Tumors, w/Expansion Cohort in Ras-Mutated Ca | Recruiting |
| NCT01781572 | Phase Ib/II | Binimetinib + Ribociclib | A Phase Ib/II Study of LEE011 in Combination With MEK162 in Patients With NRAS Mutant Melanoma | Completed |
| NCT03037385 | Phase Ib/II | BLU-667 | Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors (ARROW) | Recruiting |
| NCT01449058 | Phase Ib/II | Alpelisib + Binimetinib | A Phase Ib Study of MEK162 Plus BYL719 in Adult Patients With Selected Advanced Solid Tumors | Completed |
| NCT01885195 | Phase II | Binimetinib | MEK162 for Patients With RAS/RAF/MEK Activated Tumors | Completed |
| NCT02022982 | Phase Ib/II | Palbociclib + PD-0325901 | PALBOCICLIB + PD-0325901 for NSCLC & Solid Tumors | Active, not 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 |
| NCT03051035 | Phase I | KO-947 | First-in-Human Study of KO-947 in Non-Hematological Malignancies | Active, not recruiting |
| NCT02630420 | Phase I | Cetuximab + Savolitinib | Cetuximab and Savolitinib Treatment of Ras Wild-Type Colorectal Cancer | Withdrawn |
| NCT03091257 | Phase I | Dabrafenib + Trametinib Dabrafenib Trametinib | A Study of Dabrafenib and/or Trametinib in Patients With Relapsed and/or Refractory Multiple Myeloma | Recruiting |
| NCT04211337 | Phase III | Vandetanib Cabozantinib Selpercatinib | A Study of Selpercatinib (LY3527723) in Participants With RET-Mutant Medullary Thyroid Cancer (LIBRETTO-531) | Recruiting |
| NCT02974725 | Phase I | LXH 254 + Ribociclib LXH 254 + Trametinib LTT462 + LXH 254 | A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma | 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 |
| NCT03043313 | Phase II | Trastuzumab + Tucatinib Tucatinib | Tucatinib Plus Trastuzumab in Patients With HER2+ Colorectal Cancer | Recruiting |
| NCT01907815 | Phase II | Trametinib + Uprosertib | Trametinib and Akt Inhibitor GSK2141795 in Treating Patients With Acute Myeloid Leukemia | Terminated |
| 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 |
| NCT03637491 | Phase II | Avelumab + Binimetinib + Talazoparib Avelumab + Binimetinib | A Study of Avelumab, Binimetinib and Talazoparib in Patients With Locally Advanced or Metastatic RAS-mutant Solid Tumors | Recruiting |
| NCT03732703 | Phase Ib/II | Dexamethasone + Enasidenib + Ixazomib + Pomalidomide Cobimetinib + Dexamethasone + Ixazomib + Pomalidomide Dexamethasone + Erdafitinib + Ixazomib + Pomalidomide Dexamethasone + Ixazomib + Pomalidomide + Venetoclax Abemaciclib + Dexamethasone + Ixazomib + Pomalidomide Daratumumab + Dexamethasone + Ixazomib + Pomalidomide | Myeloma-Developing Regimens Using Genomics (MyDRUG) (MyDRUG) | Recruiting |
| NCT02747537 | Phase II | Irinotecan + Sorafenib | Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors With Sorafenib in Combination With Irinotecan | Withdrawn |
| 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 |
| NCT02648490 | Phase I | Acetaminophen + Dexamethasone + Diphenhydramine + Ondansetron HLX07 | An Open-label, Phase 1 Study to Determine the Maximum Tolerated Dose of HLX07,in Patients With Advanced Solid Cancers | Completed |
| NCT02965417 | Phase II | SYM004 | Sym004 in Metastatic Colorectal Cancer and ECD-EGFR Patients | Withdrawn |
| NCT02607813 | Phase I | LXH 254 + Spartalizumab LXH 254 | Phase I Study of LXH254 in Patients With Advanced Solid Tumors Haboring MAPK Pathway Alterations | Recruiting |
| 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 |
| 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 |
| NCT02140840 | Phase II | Trametinib | A Phase II Open-Label, Multiple-Dose, Single Agent Study to Evaluate the Overall Response Rate of Orally Administered Trametinib | Withdrawn |
| NCT03162627 | Phase I | Olaparib + Selumetinib | Selumetinib and Olaparib in Solid Tumors | Recruiting |
| NCT03613532 | Phase I | Busulfan + Fludarabine + Venetoclax | Venetoclax Added to Fludarabine + Busulfan Prior to Transplant for AML, MDS, and MDS/MPN | Recruiting |
| NCT02285439 | Phase Ib/II | Binimetinib | Phase I/II Study of MEK162 for Children With Ras/Raf Pathway Activated Tumors | Recruiting |
| 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 | Recruiting |