Bemarituzumab
Детермінований перегляд YAML-сутності з джерельної бази. Клінічний авторитет лишається за вказаними source ID та статусом клінічного sign-off.
| ID | DRUG-BEMARITUZUMAB |
|---|---|
| Тип | Препарат |
| Синоніми | Бемаритузумаб |
| Статус | переглянуто 2026-05-07 | очікує клінічного підпису |
| Хвороби | DIS-GASTRIC |
| Джерела | SRC-FIGHT SRC-FORTITUDE-101 SRC-NCCN-GASTRIC-2025 |
Дані про препарат
| Клас | Anti-FGFR2b Fc-engineered (afucosylated) humanized IgG1 monoclonal antibody |
|---|---|
| Механізм дії | Humanized IgG1 monoclonal antibody (development name FPA144) selective for the IIIb splice isoform of fibroblast growth factor receptor 2 (FGFR2b) extracellular domain. Two complementary modes of action: (1) competitive blockade of FGF7 / FGF10 / FGF22 ligand binding to FGFR2b, suppressing downstream MAPK/PI3K signaling in tumor cells that overexpress FGFR2b; (2) Fc engineering — afucosylated IgG1 glycoform with enhanced FcγRIIIa binding — produces amplified antibody-dependent cellular cytotoxicity (ADCC) by NK cells against FGFR2b-expressing tumor cells. Selectivity for the IIIb splice isoform avoids broader pan-FGFR receptor blockade and reduces the hyperphosphatemia / nail / mucosal toxicities characteristic of small-molecule pan-FGFR inhibitors. FGFR2b overexpression occurs in ~30% of HER2-non-positive gastric/GEJ adenocarcinoma; the validated companion diagnostic (Ventana FGFR2b Rx... |
| Типове дозування | FORTITUDE-101 / FORTITUDE-102 protocol: 15 mg/kg IV q2w with an additional 7.5 mg/kg loading dose on cycle 1 day 8 (administered with mFOLFOX6 backbone for FGFR2b-overexpressing 1L gastric/GEJ). Infusion over ≥30 minutes; subsequent infusions may shorten if first cycle tolerated. Treatment continued until disease progression, unacceptable toxicity (most commonly grade ≥3 corneal events), or patient withdrawal. No FDA / EMA labelled dose as of 2026-05-07 (investigational). |
| Зареєстровано в Україні | False |
| Відшкодовується НСЗУ | False |
| Остання перевірка для України | 2026-05-07 |
Нотатки
First-in-class IIIb-selective afucosylated anti-FGFR2b mAb (Amgen; development name FPA144). FDA Breakthrough Therapy Designation awarded April 2021 for FGFR2b-overexpressing 1L gastric/GEJ. Pivotal evidence: FIGHT phase 2 (Wainberg et al. Lancet Oncol 2022; bemarituzumab + mFOLFOX6 vs placebo + mFOLFOX6 in FGFR2b ≥10% 2+/3+ subgroup — mPFS 9.5 vs 7.4 mo, HR 0.68); FORTITUDE-101 phase 3 (Rha et al. ESMO 2025 LBA10; NCT05052801) — primary analysis (median follow-up 11.8 mo): mOS 17.9 vs 12.5 mo (HR 0.61, p=0.005); mPFS 8.6 vs 6.7 mo. Updated descriptive analysis (median follow-up 19.4 mo) showed mOS 14.5 vs 13.2 mo (HR 0.82) — early survival gain attenuated, raising practice-changing controversy at ESMO 2025 (one discussant flagged absence of PD-1 backbone in control arm and shrinking median OS difference). Ocular toxicity is the dose-defining AE (~70% any-grade corneal events, ~25% G≥3, typical onset ~6 months) — mandatory baseline + serial slit-lamp ophthalmology REQUIRED before each cycle. Companion diagnostic (Ventana FGFR2b RxDx, IIIb-selective IHC) defines eligibility as 2+/3+ membranous staining ≥10% of tumor cells; FGFR2b high-positive (≥10% 2+/3+) ~30% of HER2-non-positive...
Де використовується
Regimens
REG-BEMARITUZUMAB-MFOLFOX6- Bemarituzumab + mFOLFOX6 (FORTITUDE-101) — 1L FGFR2b-overexpressing HER2-non-positive gas...