Results from the pivotal phase (Ph) 2b HERIZON-BTC-01 study: Zanidatamab in previously-treated HER2-amplified biliary tract cancer (BTC).
Notice bibliographique
Résumé
4008 Background: For patients (pts) with locally advanced/metastatic BTC who progress after first-line treatment (tx), standard tx offers limited clinical benefit with modest improvement in survival. HER2-targeted therapies have improved survival in breast and gastric cancer, but there is no approved HER2-targeted therapy for BTC. Zanidatamab (zani), a HER2-targeted bispecific antibody, has shown durable responses in a subset of pts with BTC in a Ph 1 trial. Methods: HERIZON-BTC-01, an open-label, global Ph 2b study (NCT04466891), evaluated zani (20 mg/kg IV every 2 wks) in pts with HER2-amplified, locally advanced unresectable or metastatic BTC (gallbladder cancer [GBC], intra-/extra-hepatic cholangiocarcinoma [ICC/ECC]) who had received prior gemcitabine-containing therapy; pts with prior HER2-targeted therapies were excluded. Pt cohort assignment was based on tumor immunohistochemistry (IHC) status: Cohort 1 for IHC 2+/3+ (HER2 positive), or Cohort 2 for IHC 0/1+. Tumors were assessed every 8 wks per RECIST 1.1. The primary endpoint was confirmed objective response rate (cORR) by independent central review (ICR) in Cohort 1. Secondary endpoints included other efficacy and safety outcomes. Results: Enrollment is complete with 87 pts (Cohort 1, n=80; Cohort 2, n=7) treated. Median age was 64 yrs (range, 32-79); 54% were female; 66% were Asian; 52% had GBC, 30% ICC, and 18% ECC. Pts had a median of 1 line (range, 1-7) of prior therapy in the locally advanced/metastatic setting. In Cohort 1, cORR was 41% with median duration of response (DOR) of 12.9 months (m; 95% CI: 5.95, not estimable); median study follow-up time was 12.4 m. Among the 33 responders at the data cut (10OCT2022), 49% had ongoing responses and 82% had a DOR of ≥16 wks. Median time to first response was 1.8 m (range, 1.6-5.5). Progression-free survival and overall survival are being evaluated. No responses were observed in Cohort 2. In both cohorts (N=87), tx-related adverse events (TRAEs) occurred in 72% of pts; TRAEs in ≥10% of pts were diarrhea (37%) and infusion-related reaction (33%). Gr 3 TRAEs occurred in 18% of pts, with diarrhea (4.6%) and ejection fraction (EF) decreased (3.4%) in >3% of pts. Two pts (2.3%) discontinued zani due to an AE (EF decreased and non-infectious pneumonitis). Seven pts had serious TRAEs; no AE preferred term occurred in >1 pt. No zani-related Gr 4 AEs or deaths were reported. Conclusions: Results of the pivotal HERIZON-BTC-01 study indicate that the HER2 bispecific antibody zani demonstrates rapid, durable responses with a manageable safety profile in pts with tx-refractory HER2-positive BTC. Given these data, zani continues to be developed as a tx option in HER2-positive BTC. Clinical trial information: NCT04466891 . [Table: see text]
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,004 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,005 | 0,001 |
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 source (Gemma direct ou Codex distillé), 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 ».