Table 1.
Notable published clinical trials of FGFR inhibitors in advanced cholangiocarcinoma.
| Trial, Setting, References | n, FGFR Alterations | Primary Endpoint | Findings |
|---|---|---|---|
| Pemigatinib (ATP-competitive mechanism, selective for FGFR1-3) | |||
| FIGHT-202 (NCT02924376, Phase II), CCA, ≥1 previous systemic therapy [34] | n = 107 FGFR2 fusions or rearrangements, n = 20 other FGF/FGFR alterations, n = 18 with no FGF/FGFR alterations, n = 1 undetermined status | ORR |
FGFR2 fusions/rearrangements: ORR 35.5% (95% CI 26.5–45.4) including 3 CRs, 35 PRs; mPFS 6.9 months (95% CI 6.2–9.6) Other FGFR/FGF alterations: 0% ORR, mPFS 2.1 months (95% CI 1.2–4.9) No FGF/FGFR alterations: 0% ORR, mPFS 1.7 months (95% CI 1.3–1.8) |
| Infigratinib [BGJ398] (ATP-competitive mechanism, selective for FGFR1-3) | |||
| NCT02150967 (Phase II), CCA, ≥1 previous systemic therapy, FGFR2 fusions or rearrangements [35,36,37] | n = 83 FGFR2 fusions, n = 25 FGFR rearrangements | ORR | ORR 23.1% (95% CI 15.6–32.2); mPFS 7.3 months (95% CI 5.6–7.6); mDOR 5.0 months (range 0.9–19.1) |
| Derazantinib (ATP-competitive mechanism, selective for FGFR1-3) | |||
| ARQ 087-101 (NCT01752920, Phase I/II), iCCA, ≥1 previous systemic therapy or ineligible for first-line chemotherapy [38,39] | n = 29 FGFR2 fusions; n = 6 FGFR2 mutations/amplifications; n = 9 no FGFR2 alterations | Safety and tolerability |
FGFR2 fusions: ORR 20.7% (0 CRs, 6 PRs); mPFS 5.7 months (95% CI 4.0–9.2) FGFR2 mutations/amplifications: 0% ORR, mPFS 6.7 (95% CI 1.0–14.7) No FGFR2 alterations: 0% ORR, mPFS 1.5 (95% CI 0.7–N/A) |
| Debio 1347 (ATP-competitive mechanism, selective for FGFR1-3) | |||
| NCT1948297 (Phase I), advanced solid malignancies harboring activating FGFR alterations. Included 9 iCCA patients (1–3 prior lines of systemic therapy) [40,41] | n = 5 FGFR2 translocations, n = 1 FGFR1 translocation, n = 1 FGFR2 mutation, n = 1 FGFR2 activating deletion, n = 1 FGFR3 mutation | Safety and tolerability | 2/9 PR, 4/9 stable disease |
| Futibatinib [TAS-120] (covalent irreversible mechanism, selective for FGFR1-4) | |||
| FOENIX-101 (NCT02052778, Phase I), 45 CCA patients (41 iCCA), ≥1 prior systemic therapies (13 received prior reversible FGFR inhibitors) [42] | n = 28 FGFR2 gene fusions, n = 17 other FGF/FGFR alterations | Safety and tolerability | ORR 25% (7/28) in the FGFR2 gene fusion patients and 17.6% (3/17) in those with other alterations; 30.8% ORR (4/13) in patients who had previously been treated with other FGFR inhibitors; Overall DCR 79% |
| FOENIX-CCA2 (NCT02052778, Phase II), iCCA patients with FGFR2 fusions/other rearrangements, ≥1 prior systemic therapy, no prior FGFR inhibitor, ECOG PS 0/1 [43,44] | n = 55 FGFR2 fusions; n = 12 other FGFR2 rearrangements | ORR | ORR 37.3%; mPFS 7.2 months; mDOR 8.3 months; DCR 82.1% |
| Erdafitinib (ATP-competitive mechanism, selective for FGFR1-4) | |||
| NCT01703481 (Phase I), patients with advanced solid tumors for which standard therapy failed [45,46] | Within cohort of 11 CCA patients: n = 3 FGFR mutations, n = 8 FGFR fusions | Safety and tolerability | CCA patients: ORR 27.3% (95% CI 6–61); mPFS 5.1 months (95% CI 1.6–16.4); mDOR 12.9 months (n = 3) |
| LUC2001 (NCT02699606, Phase IIa), Asian patients with advanced CCA with FGFR alterations [47] | n = 8 FGFR2 fusions, n = 3 FGFR2 mutations, n = 1 FGFR3 fusion, n = 2 FGFR3 mutations | ORR | Out of 12 response-evaluable patients: ORR 50%; mPFS 5.59 months (95% CI: 1.87–13.67); mDOR 6.83 months (95% CI: 3.65–12.16); DCR 83.3% |
FGFR, fibroblast growth factor receptor; FGF, fibroblast growth factor; CCA, cholangiocarcinoma; iCCA, intrahepatic cholangiocarcinoma; ORR, overall response rate; CR, complete response; PR, partial response; mPFS, median progression-free survival; mDOR, median duration of response; DCR, disease control rate; CI, confidence interval; ECOG PS, Eastern Cooperative Oncology Group Performance Status.