Table 1 Clinical trials assessing the efficacy of combinations with immunotherapies in cancers with RAS mutations
From: Cancer immune evasion through KRAS and PD-L1 and potential therapeutic interventions
Trial | Disease | Pathway/Target | Treatment | Status |
|---|---|---|---|---|
Checkmate 568 (NCT02659059) | NSCLC | PD-1 CTLA-4 DNA cross-linking | Nivolumab Ipilimumab Platinum Doublet Chemotherapy (Carboplatin + Paclitaxel and Cisplatin + Pemetrexed) | Complete |
NCT03581487 | NSCLC | MAPK/MEK PD-1 CTLA-4 | Selumetinib Durvalumab Tremelimumab | Recruiting |
NCT03600701 | NSCLC | PD-L1 MAPK/MEK | Atezolizumab Cobimetinib | Recruiting |
KRYSTAL-1 (NCT03785249) | KRAS G12C Advanced/Metastatic solid tumours | KRAS G12C PD-1 MAPK/EGFR ErbB family protein kinases | MRTX849 (adagrasib) Pembrolizumab Cetuximab Afatinib | Recruiting |
KRYSTAL-7 (NCT04613596) | Advanced/Metastatic NSCLC | KRAS G12C PD-1 | MRTX849 Monotherapy MRTX849 in Combination with Pembrolizumab | Recruiting |
CodeBreak 100 (NCT03600883) | KRAS G12C Advanced solid tumours | KRAS G12C PD-1/L1 | Sotorasib Anti-PD-1/PD-L1 Midazolam | Active, not recruiting |
CodeBreak 101 (NCT04185883) | KRAS G12C Advanced solid tumours | KRAS G12C PD-1 MAPK/MEK MAPK/SHP2 ErbB family protein kinases MAPK/EGFR DNA cross-linking Purine synthesis /Thymidylate synthase Microtubular depolymerization and bcl-2 gene expression PD-L1 PI3K/mTOR CDK4/6 MAPK/VEGF | Sotorasib AMG-404 Trametinib RMC-4630 Afatinib Pembrolizumab Panitumumab Carboplatin Pemetrexed Docetaxel Atezolizumab Everolimus Palbociclib MVASI (bevacizumab-awwb) TNO155 FOLFIRI FOLFOX Loperamide | Recruiting |
NCT05389514 | KRAS G12V Mutant Advanced Epithelial Cancers | Cross-linking of DNA DNA synthesis inhibition PD-1 | Cyclophosphamide Gemcitabine Pembrolizumab Cell Infusion of T cells expressing HLA-DRB1*07:01-restricted KRAS G12V reactive T-cell receptors | Recruiting/ Available |
NCT04620330 | NSCLC with KRAS G12V and BRAF Activating Mutation | MAPK/Dual RAF and MEK inhibitor p53 pathway/FAK Inhibitor | VS-6766 Monotherapy VS-6766 and Defactinib in combination | Recruiting |
NCT03146962 | RAS or BRAF driven Colorectal, Pancreatic and Lung Cancers | Oxidative stress pathway/ NRF2 | High dose Ascorbic Acid infusion | Recruiting |
NCT04919369 | Metastatic Lung Non-Small Cell Carcinoma Recurrent Lung Non-Small Cell Carcinoma Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8 | KEAP1-NRF2/tBHQ-ARE PD-L1 | Tretinoin/ All-Trans Retinoic Acid (ATRA) Atezolizumab | Recruiting |
NCT01347866 | Advanced cancer | PI3K/mTOR MAPK/MEK Topoisomerase I | PF-05212384 PD-0325901 Irinotecan | Active, not recruiting |
NCT03514121 | Advanced Solid Tumours Breast Cancer Ovarian Cancer Endometrial Cancer | B7-H4 PD-1 | FPA150 Pembrolizumab | Complete |
NCT05082610 | Metastatic and Advanced Solid Tumours in Non-small Cell Lung Cancer Triple Negative Breast Cancer Malignant Neoplasm | VISTA PD-1 | HMBD-002 Pembrolizumab | Recruiting |
NCT02908672 | Melanoma | PD-L1 MAPK/MEK BRAF | Atezolizumab Cobimetinib Vemurafenib | Active, not recruiting |