A phase II trial to evaluate the epithelial-to-mesenchymal (EMT) inhibitor sotevtamab combined with docetaxel in patients with metastatic non-small cell lung cancer following failure of primary chemoimmunotherapy.
Notice bibliographique
Résumé
8577 Background: Sotevtamab is an investigational humanized monoclonal antibody that binds to tumor associated secreted clusterin (TA-sCLU). TA-sCLU is a potent inducer of the epithelial-to-mesenchymal transition (EMT), a process known to contribute to tumor invasion, metastasis, chemoresistance and immune evasion. Sotevtamab abrogates the EMT-promoting activity of TA-sCLU by inhibiting its ability to be internalized in cancer cells. Methods: An open-label, single-arm, multi-center Phase II clinical study of sotevtamab administered in combination with docetaxel was performed in subjects with metastatic non-small cell lung cancer who had experienced progression following frontline immunochemotherapy. 35 subjects were enrolled from March 2021 to November 2022 and the study was completed in December 2023. Sotevtamab was administered at a dose of 12 mg/kg once weekly on Days 1, 8 and 15 combined with docetaxel at a dose of 75 mg/m2 once every 3 weeks on Day 1. One cycle of treatment consisted of 21 days. The primary objectives were to determine the objective response rate (ORR) and the safety and tolerability of the combination. Tumor biopsies were performed prior to study initiation and after two cycles of therapy for pharmacodynamicevaluation. Results: As per interim data obtained from a rolling database lock performed in February 2023, the mean subject age was 63 and 22 patients (63%) were female. Of the 35 subjects, 28 were diagnosed with adenocarcinoma, 6 with squamous cell carcinoma and 1 with adenosquamous carcinoma; 11 were ECOG 0, 22 ECOG 1 and 2 ECOG 2. Six subjects with adenocarcinoma had a partial response for an ORR of 17.1%. Stable disease (SD) was experienced in an additional 10 subjects (9 adenocarcinomas and one squamous cell carcinoma) for an SD rate of 28.6%. The observed responses were sustained with a median duration of over one year (405 days). The estimated one-year survival rate was 33.9%. The most frequent adverse events were fatigue, infusion related reaction (IRR), diarrhea, nausea and anemia. The incidence of IRR was significantly decreased following the implementation of a premedication protocol. Analysis of paired tumour biopsies revealed in certain patients that sotevtamab induced a strong intratumoral immune response with the formation of Tertiary Lymphoid Structures (TLS). Various pharmacodynamic evaluations are being performed to better define the profile of responding patients. Conclusions: This phase II study showed promising response and overall tumor control. Duration of response was particularly encouraging and relevant to further exploration. The sotevtamab and docetaxel combination may enhance immune-mediated anti-tumor response through induction of TLS. Data from the final database lock will be presented. Clinical trial information: NCT04364620 .
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 | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,001 |
| Méta-épidémiologie (sens large) | 0,002 | 0,001 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| 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) | 0,003 | 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 ».