Efficacy of derazantinib in intrahepatic cholangiocarcinoma patients with FGFR2 mutations or amplifications: Interim results from the phase 2 study FIDES-01.
Notice bibliographique
Résumé
427 Background: Derazantinib, a potent anti- FGFR1-3 oral kinase inhibitor, has shown clinically meaningful anti-tumor activity (21%), durable responses (median, 6.4 months), and progression-free survival (median, 8.0 months) in patients (pts) with FGFR2 fusion (FGFR2 F )-positive intrahepatic cholangiocarcinoma (iCCA), and with a manageable toxicity profile. Herein, we report an interim analysis of the clinical efficacy data of derazantinib for pts with iCCA harboring FGFR2 mutations or amplifications (FGFR2 M/A ), a potential therapeutic option currently not addressed by FGFR inhibitors. Methods: Study FIDES-01 enrolls in a dedicated cohort pts with FGFR2 M/A+ advanced iCCA who received previous chemotherapy. Pts receive 300 mg derazantinib daily until disease progression, death or intolerance. The primary endpoint is the proportion of pts alive and free of disease progression at 3 months (PFS3; RECIST 1.1, central imaging review) using a Simon’s two-stage sample-size minimizing statistical design. The interim analysis population comprises 23 pts dosed (intention to treat) who had at least one post-baseline tumor assessment (or clinical progression, or died) by June 3, 2021, using investigator assessments based on RECIST 1.1. Results: To date, 28 pts have been enrolled and dosed. FGFR2 M/A observed in these pts included missense point mutations (78%), other short variants (11%) and amplifications (11%). Transition from stage 1 to stage 2 of the study was achieved earlier than planned after 8 (67%) of 12 pts were assessed as PFS3 based on central imaging review. In 23 pts included in this interim analysis for efficacy, the best overall response (investigator assessment) was confirmed partial response in two (8.7%) and stable disease in additional 15 pts (65.2%), resulting in a disease control rate of 73.9% (95% CI, 51.6–89.8). Using Kaplan-Meier analyses, the median PFS was 7.3 months (95%CI, 3.5–16.7) and the probability of being progression-free at 3 months and at 6 months were 76.3% (95%CI, 51.9–89.4) and 50.3% (95%CI, 21.7–73.4), respectively. Clinically meaningful anti-tumor efficacy was observed across all types of genetic aberrations. The safety profile of derazantinib in FGFR2 M/A+ iCCA pts was consistent with that previously reported for FGFR2 F+ iCCA pts. Conclusions: This interim data in study FIDES-01 suggest that derazantinib treatment provides clinical benefit to pts with advanced iCCA harboring FGFR2 M/A who progressed after at least one line of standard chemotherapy. To our knowledge, this is the first report of clinically meaningful anti-tumor efficacy in a prospectively planned cohort of iCCA pts harboring FGFR2 M/A . The study is ongoing to accrue 43 patients, assessing derazantinib as a therapeutic option for FGFR2 M/A+ iCCA pts after disease progression on first-line treatment. Clinical trial information: NCT03230318.
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Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,002 | 0,006 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».