Early results of intratumoral INT230-6 alone or in combination with ipilimumab in subjects with advanced sarcomas.
Notice bibliographique
Résumé
11557 Background: Patients have limited treatment options following initial chemotherapy failure. INT230-6, a novel formulation of cisplatin (CIS) and vinblastine (VIN) with an amphiphilic cell penetration enhancer, is designed for intratumoral (IT) administration. Study IT-01 (BMS # CA184-592, NCT 03058289) evaluates INT230-6 alone or in combination with ipilimumab (IPI), an antibody to CTLA-4. INT230-6 dosing is set by a % of the volume of the tumor to be injected. The product has been shown to disperse throughout an injected tumor and diffuse into cancer cells. Cell death leads to recruitment of dendritic and T cells, the effect of which may be augmented by CTLA-4 inhibition as evidenced by increased efficacy of the combination in preclinical models. Historically, checkpoint inhibitors have limited activity in sarcoma. Considering the large volume of drug injected and retained in the tumor, coupled with immune infiltration on biopsies, RECIST response methodology may not capture the benefits of INT230-6 treatment. Methods: IT-01 is an open-label phase 1/2 study that is enrolling adult subjects with locally advanced, unresectable or metastatic sarcoma. INT230-6 was administered IT Q2W for 5 doses alone or with IPI 3mg/kg IV Q3W for 4 doses. The study objectives are to assess the safety and efficacy of IT INT230-6 alone and in combination with IPI. Results: 16 heterogenous sarcoma subjects (13 monotherapy, 3 IPI combination) having a median of 3 prior therapies (0, 8) were enrolled to date. The INT230-6 dose was up to 145 mL (72.5 mg of CIS, 14.5 mg VIN) in a single session (an amount of each agent in excess of standard IV doses). The most common ( > 20%) related TEAEs in sarcoma subjects (n = 16) were localized pain (63%), fatigue (38%), decreased appetite (31%), nausea (31%), and vomiting (25%) most of which were low grade; with only grade 3 TEAE above 5% being anemia (13%). There were no related grade 4 or 5 TEAEs. In 11 evaluable monotherapy subjects, the disease control rate (DCR = CR+PD+SD) was 82%. Basket studies of sarcomas, including chordoma, with Royal Marsden Hospital index (RMHI) scores of 2 or higher report median overall survival (mOS) of 4 months. In this study 75% of monotherapy subjects had a RMHI score of 2 and preliminary estimates of mOS was 21.3 (4.67, NA) months. Pilot immunohistochemistry analysis of 5 paired (pre- and 28 days post-dose) biopsy samples showed substantial tumor necrosis, reduction of viable cancer, a decreased cancer proliferation as measured by Ki67, and increased TILs. Conclusions: Preliminary data shows that INT230-6 administered intratumorally alone or in combination with ipilimumab is well-tolerated in this small, heterogenous sarcoma population. The preclinical cancer cell death and immune infiltration mechanism of action appears to translate to sarcoma subjects. There are early signs of efficacy, DCR and potentially OS, that need to be confirmed in randomized studies. Clinical trial information: 03058289.
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) | 0,001 | 0,001 |
| 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) | 0,003 | 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 ».