Table 1.
Ongoing RAS inhibitor trials
| Study/Phase | Drug | Disease | Biomarker | Clinicaltrials.gov registration no. | |
| Direct RAS inhibitors | |||||
| A phase I/II, study evaluating the safety, tolerability, PK, and efficacy of AMG 510 in subjects with solid tumours with a specific KRAS mutation (CodeBreak 100) | AMG510 | Advanced/Metastatic solid tumours | KRASG12C Mutant | NCT03600883 | |
| A Phase 1b, Protocol Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 510 (pINN) Sotorasib Monotherapy and in Combination with Other Anti-cancer Therapies in Subjects with Advanced Solid Tumours With KRAS p.G12C Mutation (CodeBreak 101) | AMG510 PD1 inhibitor MEK inhibitor SHP2 allosteric inhibitor Pan-ErbB TKI PD-L1 inhibitor EGFR inhibitor Chemotherapy |
Advanced/Metastatic solid tumours | KRASG12C Mutant | NCT04185883 | |
| Phase I/II Study of MRTX849 in patients having a KRAS G12C Mutation KRYSTAL-1 | MRTX849 | Advanced/Metastatic solid tumours | KRASG12C Mutant | NCT03785249 | |
| First-in-Human Study of JNJ-74699157 in participants with Tumours Harboring the KRAS G12C Mutation | JNJ-74699157 (ARS-3248) | Advanced/Metastatic solid tumours | KRASG12C Mutant | NCT04006301 | |
| A Phase I/II study of LY3499446 administered to patients with advanced solid tumours with KRAS G12C mutation | LY3499446 Abemaciclib Cetuximab Erlotinib docetaxel |
Advanced/Metastatic solid tumours | KRASG12C Mutant | NCT04165031 | |
| A Study to evaluate the safety, Pharmacokinetics, and activity of GDC-6036 in participants with advanced or metastatic solid tumours with a KRAS G12C mutation | GDC-6036 | Advanced/Metastatic solid tumours | KRASG12C Mutant | NCT04449874 | |
| Indirect Targeting of RAS | |||||
| SOS inhibitor | |||||
| A study to test different doses of BI-1701963 alone and in combined with trametinib in patients with different types of advanced cancer (solid tumours with KRAS mutation) | BI-1701963 BI-3406 trametinib |
Advanced/Metastatic solid tumours | KRAS mutations | NCT04111458 | |
| SHP2 inhibitors | |||||
| Dose escalation of RMC-4630 monotherapy in relapsed/refractory solid tumours | RMC-4630 | Advanced/Metastatic solid tumours | Mutations that hyperactivate ERK pathway | NCT03634982 | |
| Dose finding study of TNO155 in adult patients with advanced solid tumours | TNO155 | Advanced/Metastatic solid tumours | EGFR or KRASG12C mutations | NCT03114319 | |
| Phase Ib study of TNO155 in combination with Spartalizumab or Ribociclib in selected malignancies | TNO155 Spartalizumab ribociclib |
Advanced/Metastatic solid tumours | KRAS mutations | NCT04000529 | |
| First-in-Human Study of the SHP2 Inhibitor BBP-398 in patients with Advanced Solid Tumours | BBP-398 | Advanced/Metastatic solid tumours | MAPK-pathway alterations (excluding BRAF V600X) | NCT04528836 | |
| Farnesyltransferase inhibitors | |||||
| Phase II study of Tipifarnib in squamous head and neck cancer with HRAS mutations | Tipifarnib | Advanced head and neck squamous cell cancer | HRAS mutations | NCT02383927 | |
| RAF inhibitors | |||||
| Phase I study of LXH254 in patients with advanced solid tumours harbouring MAPK pathway alterations | LXH-254 Anti-PD-1 antibody |
Advanced/Metastatic solid tumours | ERK pathway mutations | NCT02607813 | |
| Cobimetinib and HM95573 in Patients with Locally Advanced or Metastatic Solid Tumours | Belvarafenib cobimetinib | Advanced/Metastatic solid tumours | RAS or RAF mutation | NCT03284502 | |
| A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma | LXH-254 Trametinib LTT462 Ribociclib |
Advanced/Metastatic solid tumours | KRAS or BRAF mutant NSCLC or NRAS mutant melanoma | NCT02974725 | |
| Study of the Safety and Pharmacokinetics of BGB-283 (Lifirafenib) and PD-0325901 (Mirdametinib) in Participants with Advanced or Refractory Solid Tumors | BGB-283 PD-0325901 |
Advanced/Metastatic solid tumours | KRAS mutant NSCLC or endometrial cancer | NCT03905148 | |
| MEK inhibitors | |||||
| Trametinib and HDM201 in colorectal cancer patients with RAS/RAF mutant and TP53 wild-type advanced/metastatic colorectal cancer I | HDM201 (MDM2 inhibitor) Trametinib |
Colorectal cancer | RAS mutant and TP53 wild type | NCT03714958 | |
| Atezolizumab and Cobimetinib in Treating Patients with Metastatic, Recurrent, or Refractory Non-small Cell Lung Cancer | Cobimetinib atezolizumab | Advanced/Metastatic solid tumours | KRAS mutation | NCT03600701 | |
| Study of MK-8353 + Selumetinib in Advanced/Metastatic Solid Tumors (MK-8353-014) | Selumetinib MK-8353 |
Advanced/Metastatic solid tumours | none | NCT03745989 | |
| Trial of Trametinib and Ponatinib in Patients with KRAS Mutant Advanced Non-Small Cell Lung Cancer | Trametinib ponatinib |
Advanced/Metastatic solid tumours | KRAS mutation | NCT03704688 | |
| Trametinib and Hydroxychloroquine in Treating Patients With Pancreatic Cancer | Trametinib hydroxychloroquine |
Advanced pancreas cancer | none | NCT03825289 | |
| Trametinib and Docetaxel in Treating Patients with Recurrent or Stage IV KRAS Mutation Positive Non-Small Cell Lung Cancer | Trametinib Docetaxel |
Metastatic NSCLC | KRAS mutation | NCT02642042 | |
| ERK inhibitors | |||||
| First-in-Human Study of KO-947 in Non-Hematological Malignancies | KO-947 | Advanced/Metastatic solid tumours | BRAF, KRAS, NRAS or HRAS mutation | NCT03051035 | |
| A Study of LY3214996 Administered Alone or in Combination with Other Agents in Participants with Advanced/Metastatic Cancer | LY-3214996 | Advanced melanoma or NSCLC | BRAF or NRAS mutations | NCT02857270 | |
| Adoptive Cell therapies | |||||
| Administering Peripheral Blood Lymphocytes Transduced with a Murine T-Cell Receptor Recognizing the G12D Variant of Mutated RAS in HLA-A*11:01 Patients | Anti-RAS G12D mTCR | Advanced/Metastatic solid tumours | HLA-A11:01 RASG12D mutation | NCT03745326 | |
| Administering Peripheral Blood Lymphocytes Transduced with a Murine T-Cell Receptor Recognizing the G12V Variant of Mutated RAS in HLA-A*11:01 Patients | Anti-RAS G12D mTCR | Advanced/Metastatic solid tumours | HLA-A11:01 RASG12D mutation | NCT03190941 | |
| Vaccine therapy | |||||
| A Study of mRNA-5671/V941 as Monotherapy and in Combination with Pembrolizumab (V941-001) | mRNA-5671 | Advanced NSCLC, non-MSI-high CRC, PDAC | HLA-A11:01 and/or HLA-C08:02; KRASG12C, KRASG12D, KRASG12V or KRASG13D mutation | NCT03948763 | |
| Immunotherapy | |||||
| A study of Avelumab, Binimetinib and Talazoparib in patients with locally advanced or metastatic RAS-mutant Solid Tumors I/II | Avelumab Binimetinib Talazoparib |
Solid tumours | KRAS or NRAS mutant | NCT03637491 | |
| A study of Binimetinib + Nivolumab plus or minus Ipilimumab in patients with previously treated Microsatellite stable metastatic colorectal cancer with RAS mutation I/II | Binimetinib Nivolumab ipilimumab |
Colorectal cancer | RAS mutations | NCT03271047 | |