Table 2.
Summary of ongoing rechallenge/reintroduction trials with anti-EGFR agents.
| Study | Phase | N | Patient population | Therapy | Line | Primary endpoint | Secondary endpoint(s) | Registration number |
|---|---|---|---|---|---|---|---|---|
| VELO (65) | Phase II | 112 | RAS wt | Panitumumab + trifluridine/tipiracil vs. trifluridine/tipiracil |
3 | PFS | OS, ORR | EudraCT Number 2018-001600-12 |
| FIRE-4 (AIO KRK-0114) (66) | Phase III | 230 | RAS wt | Cetuximab + FOLFIRI vs. regorafenib | 3 | OS | RR, PFS, safety, DpR, early tumor shrinkage, biomarker analysis | NCT02934529 |
| CITRIC (67) | Phase II | 66 | RAS, BRAF, EGFR-ECD wt | Cetuximab + irinotecan | 3 | ORR | DCR, DOR, PFS, OS, safety | EudraCT Number 2020-000443-31 |
| PARERE (68) | Phase II | 214 | RAS and BRAF wt | Panitumumab > regorafenib vs. regorafenib > panitumumab |
3 | OS | PFS (1st and 2nd), TTF, ORR, safety | EudraCT Number 2019-002834-35/NCT04787341 |
| PULSE (69) | Phase II | 120 | RAS wt | Panitumumab vs. regorafenib or trifluridine/tipiracil | NS | OS | PFS, ORR, CBR, safety, QoL | NCT03992456 |
| CAPRI-2 GOIM (69) | Phase II | 200 | RAS/BRAF wt | Irinotecan + cetuximab* | ≥2 | RR | PFS, OS, safety, QoL | NCT05312398 |
| CAVE-2 GOIM (70) | Phase II | 173 | RAS/BRAF wt | Avelumab and cetuximab vs. cetuximab alone | 3 | OS | ORR, PFS, safety | NCT05291156 |
| MD Anderson Cancer Center study (USA) (65) | Phase II | 84 | RAS, BRAF, EGFR-ECD wt | Panitumumab | 3 | ORR | CR/PR/SD, PFS, OS | NCT03087071 (cohort 3) |
These trials are ongoing at the time of manuscript submission. *RAS mt patients received trifluridine/tipiracil or regorafenib.
CBR, Clinical benefit rate; CR, complete remission; DCR, disease control rate; DOR, duration of response; DpR, depth of response; ECD, extra-cellular domain; EGFR, epidermal growth factor receptor; mt, mutant; NS, not specified; ORR, overall response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; PR, partial remission; QoL, quality of life; RR, response rate; SD, stable disease; TTF, time to failure; wt, wild-type.