Antitumor activity and safety of dostarlimab monotherapy in patients with mismatch repair deficient non-endometrial solid tumors: A post-hoc subgroup analysis of patients with colorectal cancer.
Notice bibliographique
Résumé
201 Background: Dostarlimab is a programmed death receptor-1 (PD-1) blocking antibody that is approved in the US as a monotherapy in adult patients (pts) with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing regimen or dMMR recurrent or advanced solid tumors that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. Here, we report on the antitumor activity and safety of dostarlimab monotherapy in pts with dMMR colorectal cancer (CRC), a post-hoc subgroup analysis of cohort F of the GARNET trial. Methods: GARNET is a phase 1, multicenter, open-label, single-arm study of dostarlimab monotherapy in pts with advanced or recurrent solid tumors. Cohort F of the GARNET expansion cohorts enrolled pts with dMMR/MSI-H or POLε mutated non-endometrial solid tumors, including pts with CRC. Pts must have progressed per blinded independent central review (BICR) following prior systemic therapy for advanced disease. Pts with CRC were required to have progressive disease after or been intolerant to fluoropyrimidine, oxaliplatin, and irinotecan. Pts received 500 mg intravenous dostarlimab every 3 weeks for 4 cycles, followed by 1000 mg every 6 weeks until discontinuation. Primary endpoints were objective response rate (ORR) and duration of response by BICR per RECIST v1.1. Pts were included in the efficacy analysis if they received ≥1 dose of dostarlimab, had measurable disease at baseline, and had ≥24 weeks of follow-up. All pts who received ≥1 dose of dostarlimab were included in the safety analysis. Results: As of the March 01, 2020 interim analysis data cut, 141 pts with dMMR non-endometrial solid tumors were included in the safety analysis, with 106 in the efficacy analysis. Of the pts in the efficacy analysis, 69 (65.1%) had CRC. Confirmed ORR by BICR per RECIST v1.1 in pts with dMMR CRC was 36.2% (95% CI, 25.0%–48.7%). There were 3 complete responses and 22 partial responses. At the data cut, 23 pts (92%) were still on treatment. Median duration of response had not been reached for pts with CRC. In the overall dMMR non-endometrial solid tumor population, treatment-related adverse events (TRAEs) were reported in 68.1% of pts, with 8.5% of pts experiencing at least 1 grade ≥3 TRAE. The most common grade ≥3 TRAE was lipase increased in 2 (1.4%) of pts. Only 5 pts (3.5%) discontinued dostarlimab due to at TRAE. Treatment-related serious AEs were reported in 9 (6.4%) pts. Conclusions: Dostarlimab demonstrated durable clinically meaningful antitumor activity in pts with dMMR CRC, which was consistent with that seen in patients with dMMR non-CRC solid tumors. No new safety signals were detected in patients with dMMR non-endometrial solid tumors. Clinical trial information: NCT02715284.
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 | 0,002 | 0,002 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,004 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,002 | 0,000 |
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 ».