Abstract CT142: A phase I open-label, dose escalation study of a novel peptide (SOR-C13) antagonistic to the TRPV6 ion channel in patients with advanced solid tumor cancers
Notice bibliographique
Résumé
Abstract Background: SOR-C13 is a first-in-man selective peptide inhibitor of Transient Receptor Potential Vanilloid 6 (TRPV6) calcium oncochannel. TRPV6 is highly expressed in carcinomas including prostate, breast, lung and ovary and expression is correlated with poor outcomes. TRPV6-mediated Ca2+ entry is responsible for maintaining a high proliferation rate, increasing cell survival and apoptosis resistance. Since SOR-C13 blocks TRPV6-mediated Ca2+ influx it was evaluated as a single agent in patients with late-stage carcinoma. Methods: This was a phase I, multi-center, open-label, dose escalation study to assess safety and tolerability of SOR-C13 in subjects with advanced carcinomas commonly known to express the TRPV6 channel (NCT01578564). Subjects received two 21-day cycles of treatment consisting of SOR-C13 for 3 d on/4 d off, 3 d on/11 d off (21 d/cycle). Tested doses were 1.375, 2.75, 4.13 and 6.2 mg/kg given as i.v. infusion initially over 20 m moving to 90 m. In the event of clinically meaningful response (tumor response or stable disease), additional cycles were offered to subjects. Subjects were assessed for safety, tolerability and preliminary efficacy. Results: Twenty-three subjects with advanced refractory solid tumors were in the study. No study drug-related serious adverse events occurred during the study. The most frequently reported treatment-emergent adverse events (TEAEs) were fatigue (30%), hypoalbuminemia (30%), anemia (30%), urinary tract infection (30%), blood calcium decreased (22%), decreased appetite (22%), nausea (22%), constipation (17%), aspartate aminotransferase increased (17%), cough (17%), blood alkaline phosphatase increased (13%), diarrhea (13%), hypercalcemia (13%), hyperkalemia (13%), hypocalcemia (13%). Anemia (Grade 1 to 3) was the only TEAE reflecting clinically significant hematological abnormalities. In all but one case, these events were assessed as unrelated or unlikely related to the study drug. The only safety concern identified definitely related to SOR-C13 infusion was reductions of serum calcium that were short-lived (resolved during the post-infusion observation time (4 h or within <24 h) and asymptomatic at all doses. A range of safe dosing was established between 4.13 and 6.2 mg/kg. Anti-tumor activity was observed across a wide variety of tumor types. Twelve of 22 evaluable subjects (54.5%) had stable disease after 2 cycles. The duration of response ranged from 4 to 7.5 cycles with one subject still in stable disease after 16 cycles (11 months). Two patients with advanced pancreatic cancer showed tumor reduction of 7% (4.13 mg/kg) and 27% (6.2 mg/kg) after two cycles with attendant decreases in CA 19-9. Conclusions: SOR-C13 was safe and well tolerated in subjects with advanced solid tumors of epithelial origin and demonstrates potential activity in patients with advanced solid tumor cancer. Citation Format: Siqing Fu, Hal H. Hirte, Stephen Welch, Toney T. Ilenchuk, Dominique Dugourd, Tyler Lutes, Christopher Rice, Jack M. Stewart. A phase I open-label, dose escalation study of a novel peptide (SOR-C13) antagonistic to the TRPV6 ion channel in patients with advanced solid tumor cancers. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT142.
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 | 0,000 |
| 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) | 0,004 | 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 ».