Table 2.
Recent and ongoing clinical trials investigating agents targeting the key driver mutations in CCA
| Target | Targeted agents | Study | Patient population (n) | Status | Results | NCT number |
|---|---|---|---|---|---|---|
| IDH1/2 | Ivosidenib | Phase 1, multicenter, open-label | 73 | Active, not recruiting | Ongoing | NCT02073994 |
| Phase 3, multicenter, (ClarIDHy) | 185 | Active, not recruiting | mPFS = 2.7 mos (ivosidenib) vs. mPFS = 1.4 mos (placebo) | NCT02989857 | ||
| FT2012 | Phase 1/2 | 200 (estimated) | Active, not recruiting | Ongoing | NCT03684811 | |
| BAY1436032 | Phase 1, open-label, non-randomized, multicenter | 81 | Active, not recruiting | Ongoing | NCT02746081 | |
| FGFR2 | Pemigatinib | Phase 2, open-label, single-arm, multicenter study (FIGHT-202) | 146 | Active, not recruiting | ORR = 35.5%; PFS = 6.9 mos; DoR = 7.5 mos (interim results for 107 pts) | NCT02924376 |
| Phase 3, open-label, randomized, active-controlled, multicenter (FIGHT-302) | 432 (estimated) | Recruiting | Ongoing | NCT03656536 | ||
| Infigratinib | Phase 2, single arm | 160 (estimated) | Recruiting | ORR = 14.8%; DCR = 75.4%; mPFS = 5.8 mos (interim results for 61 pts) | NCT02150967 | |
| Phase 3 multicenter, open-label, randomized (The PROOF Trial) | 384 (estimated) | Recruiting | Ongoing | NCT03773302 | ||
| Derazantinib | Phase 2, open-label, single-arm study | 143 (estimated) | Recruiting | Ongoing | NCT03230318 | |
| Futinatinib | Phase 1/2 | 386 | Active, not recruiting | ORR = 37.3%; DCR = 82.1%; mPFS = 7.2 mos; mDoR = 6.2 mos (interim results) | NCT02052778 | |
| Phase 3, open-label, randomized (FOENIX-CCA3) | 216 (estimated) | Recruiting | Ongoing | NCT04093362 | ||
| Erdatifinib | Phase 2 | 35 | Active, not recruiting | Ongoing | NCT02699606 | |
| Debio-1347 | Phase 2 basket (FUZE Clinical Trial) | 63 | Active, not recruiting | Ongoing | NCT03834220 | |
| Ponatinib | Phase 2 | 45 (estimated) | Recruiting | Ongoing | NCT02272998 | |
| NTRK | Entrectinib | Phase 2 basket, open-label, multicenter, global (STARTRK-2) | 700 (estimated) | Recruiting | Ongoing | NCT02568267 |
| Larotrectinib | Phase 2 basket (NAVIGATE) | 203 (estimated) | Recruiting | Ongoing | NCT02576431 | |
| BRAF | Dabrafenib + trametinib | Phase 2, open-label | 206 | Active, not recruiting | ORR = 47%; mDoR ≥6 mos in the 54% of responders; PFS = 7.2 mos; OS = 11.3 mos (interim results for 43 pts) | NCT02034110 |
mPFS: median progression-free survival; DCR: disease control rate; mos: months; ORR: overall response rate; DoR: duration of response; mDoR: median duration of response; pts: patients