Final analysis of a phase 1b, randomized, multicenter study of talimogene laherparepvec (T-VEC) plus pembrolizumab (pembro) combination for the treatment (Tx) of recurrent/metastatic squamous cell carcinoma of the head and neck (R/M HNSCC): MASTERKEY-232.
Notice bibliographique
Résumé
6036 Background: T-VEC, a genetically modified herpes simplex virus-1, is the first FDA- and EMA-approved oncolytic viral immunotherapy designed to enhance systemic antitumor immune responses. R/M HNSCC is a disease with considerable clinical complexity and poor prognosis. Pembro is a PD-1-specific humanized monoclonal antibody currently approved as first-line Tx for this disease, but there is an unmet need among many patients (pts). To meet this gap, the safety and preliminary efficacy of T-VEC plus pembro in pts with R/M HNSCC was evaluated in a phase 1b study (Harrington et al. Clin Cancer Res. 2020). Here, we present results of the final analysis of this study (NCT02626000). Methods: Eligible pts (≥18 yrs) had ECOG-PS of 0 or 1; histologically confirmed R/M HNSCC of the oral cavity, oropharynx, hypopharynx, or larynx unsuitable for curative surgical resection or radiotherapy; platinum-refractory and with injectable tumors. Pts with known active CNS metastases and any systemic or local therapy 28 days before enrollment were excluded. T-VEC was injected intralesionally up to 8.0 mL of 10 6 PFU/mL according to lesion sizes on day 1; after 3 weeks, subsequent doses of ≤8.0 mL of 10 8 PFU/mL were given Q3W. Pembro was given intravenously at 200 mg Q3W. Pts were followed-up for 36 mos after the last patient was enrolled in the study. Key endpoints (irRECIST per investigator assessment) were objective response rate (ORR), best overall response (BOR), disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 36 pts (80.6% male) were enrolled and treated: 28 (77.8%) had confirmed PD-L1-positive tumor (CPS ≥1), 5 (13.9%) were HPV-positive, 13 (36.1%) had metastatic disease, and 19 (52.8%) had prior lines of therapy in the R/M setting. At the final analysis, 7 pts (19.4%) completed the study, and 29 (80.6%) discontinued the study due to death. Safety profile was consistent with that at 1-yr analysis (Harrington et al. Clin Cancer Res. 2020). Confirmed ORR was seen in 16.7% (95% CI, 6.4–32.8). No patient had a complete response as their BOR, 6 (16.7%) had a partial response, 8 (22.2%) had stable disease, 6 (16.7%) had progressive disease, 6 (16.7%) were unevaluable, and 10 (27.8%) died before the first response assessment. The DCR was 38.9% (95% CI, 23.1–56.5). The median DOR was 45.9 mos (95% CI, 8.5–NE). The median PFS was 3.0 mos (95% CI, 2.0–5.8), and the median OS was 5.8 mos (95% CI, 2.9–11.4). Conclusions: The safety results at 3 yrs for T-VEC plus pembro in pts with R/M HNSCC were consistent with those of the 1-yr analysis. Although the response rate was consistent with that observed with pembro alone in historical HNSCC studies, the extended DOR in responding patients warrants further investigation. Clinical trial information: NCT02626000.
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 | 0,005 | 0,003 |
| Méta-épidémiologie (sens strict) | 0,002 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,002 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,008 | 0,002 |
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 ».