Table 2.
Selected past and ongoing prospective clinical trials on targeted therapy and immunotherapy in BRAF V600E metastatic CRC.
| Trial | Phase | Sample size | Treatment arm(s) | Line of treatment (and MSI status) | ORR (%) | mPFS (months) | mOS (months) |
|---|---|---|---|---|---|---|---|
| Combined BRAF, EGFR ± MEK inhibition | |||||||
| Yaeger et al.84 | I | 15 | Vemurafenib + panitumumab | ⩾2L | 13 | 3.2 | 7.6 |
| Corcoran et al.89 | I | 20 | Dabrafenib + panitumumab | ⩾1L | 10 | 3.5 | 13.2 |
| 91 | Dabrafenib + panitumumab + trametinib | ⩾1L | 21 | 4.2 | 9.1 | ||
| BEACON CRC85 | III | 220 | Encorafenib + cetuximab (versus cetuximab + irinotecan-based chemotherapy) | ⩾2L | 19.5 (versus 1.8) | 4.3 (versus 1.5) | 9.3 (versus 5.9) |
| 224 | Encorafenib + cetuximab + binimetinib (versus cetuximab + irinotecan-based chemotherapy) | ⩾2L | 26.8 (versus 1.8) | 4.5 (versus 1.5) | 9.3 (versus 5.9) | ||
| ANCHOR CRC87 (NCT03693170) | II | 92 | Encorafenib + cetuximab + binimetinib | 1L | 47.8 | 5.8 | 17.2 |
| BREAKWATER (NCT04607421) | III | 765 (in 3 arms) | Encorafenib + cetuximab versus encorafenib + cetuximab + FOLFOX (versus bevacizumab + FOLFOX/FOLFIRI/XELOX) | 1L | – | – | – |
| Immunotherapy plus BRAF doublet inhibition | |||||||
| Corcoran et al.92 | II | 20 | Dabrafenib + trametinib + spartalizumab | Unspecified (MSI-unselected) | 35 | – | – |
| Morris et al.93 | II | 23 | Encorafenib + cetuximab + nivolumab | ⩾2L (MSS patients) | 48 | 7.4 | 15.1 |
| SWOG 2107 (NCT05308446) | II | 84 (in 2 arms) | Encorafenib + cetuximab + nivolumab (versus encorafenib + cetuximab) | ⩾2L (MSS patients) | – | – | – |
| SEAMARK (NCT05217446) | II | 104 (in 3 arms) | Encorafenib + cetuximab + pembrolizumab (versus pembrolizumab alone) | 1L (MSI-high patients) | – | – | – |
| Combined BRAF, EGFR and PI3K inhibition | |||||||
| Tabernero et al.94 | II | 52 | Encorafenib + cetuximab + alpelisib (versus encorafenib + cetuximab) | ⩾2L | 27 (versus 22) | 5.4 (versus 4.2) | 15.2 (versus not reached) |
| BRAF and EGFR inhibition plus irinotecan | |||||||
| SWOG S140690 | II | 50 | Vemurafenib + cetuximab + irinotecan versus cetuximab + irinotecan | 2L/3L | 17 (versus 4) | 4.2 (versus 2.0) | 9.6 (versus 5.9) |
BRAF, serine/threonine-protein kinase B-Raf; CRC, colorectal cancer; EGFR, epidermal growth factor receptor; MEK, mitogen-activated protein kinase kinase; mOS, median overall survival; mPFS, median progression-free survival; MSI, microsatellite instability; MSS, microsatellite stability; ORR, objective response rate; PI3K, phosphoinositide 3-kinase.