INT230-6 monotherapy and in combination with ipilimumab (IPI) across a broad spectrum of refractory soft tissue sarcomas (STS) [Intensity IT-01; BMS#CA184-592].
Notice bibliographique
Résumé
11515 Background: INT230-6 is a novel intratumoral (IT) agent with a dual anti-cancer mechanism (tumor cytoreduction while stimulating antigen presentation and recruitment of T-cells). The drug is comprised of cisplatin (CIS) and vinblastine (VIN) co-formulated with an amphiphilic molecule that enables drug dispersion throughout tumors and passive diffusion into cancer cells following IT delivery. In the neoadjuvant setting, a single injection can cause necrosis in > 95% of the tumor and recruit TILs. Combining with anti-CTLA-4 improved responses in preclinical models. Methods: INT230-6 dose is set by the tumor’s longest diameter and is proportional to the injected disease volume. INT230-6 is administered IT Q2W for 5 treatment sessions followed by maintenance every 9 weeks as monotherapy or with IPI 3mg/kg IV Q3W for 4 doses. Biopsies from injected tumors are obtained pretreatment and Day 28 for immunoprofiling. Results: 22 subjects with various advanced STS histologies with a median age of 64 and a median of 3 prior systemic therapies were enrolled (11 INT230-6 alone, 11 IPI combination). There were 178 image-guided IT INT230-6 injections (107 to deep tumors) at INT230-6 doses ranging from 5 to 242 mL (121mg CIS, 24.2mg VIN, doses which vastly exceed the usual IV doses of these drugs). PK analysis showed that > 95% of drug agents remain in the tumor. The most common (> 25%) all-grade related adverse events (AEs) in evaluable monotherapy subjects (n = 10) were pain (80%), decreased appetite (40%), nausea (40%), anemia (30%), fatigue (30%) and vomiting (30%). Tolerability was similar for the combination with IPI. Most events were low grade. The incidence of grade 3 AEs for the INT230-6 arm was 30% and for the IPI combination was 10%. There were no related grade 4 or 5 AEs in either cohort. RECIST metrics may not accurately reflect clinical benefit with this treatment given large volumes of INT230-6 is repeatedly injected into a tumor and local inflammation may occur. Paired biopsies showed reduction in proliferating tumor cells and an increase in T-cell infiltrates. The disease control rate at the first imaging timepoint for evaluable INT230-6 subjects (n = 9) was 56% and for evaluable IPI combination (n = 5) was 80%. Abscopal effects were seen in 2 monotherapy subjects, though most uninjected tumors were not tracked. The estimated 1-year overall survival was 88% for the IPI combo and 60% for the monotherapy cohort. Conclusions: IT INT230-6 is well tolerated as monotherapy and combined with IPI. STS, which is typically not sensitive to immunotherapy, may be amenable to INT230-6 or IPI combo to create antigens and promote a systemic immune response. Preliminary efficacy using INT230-6 alone is encouraging and will be evaluated in a global phase 3 trial. Further evaluation is needed to determine whether the addition of IPI may improve patient outcomes. Clinical trial information: NCT03058289.
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 | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 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 ».