Pembrolizumab, maveropepimut-S, and low-dose cyclophosphamide in advanced epithelial ovarian cancer: Results from phase 1 and expansion cohort of PESCO trial.
Notice bibliographique
Résumé
5505 Background: Platinum-resistant ovarian cancer (PROC) continues to have a poor prognosis. Maveropepimut-S (MVP-S, namely DPX-Survivac) leverages the lipid-based DPX delivery platform to educate a specific and persistent T cell-based immune response to 5 HLA-restricted peptides from survivin, a cancer-related protein commonly upregulated in several cancers. MVP-S in combination with Pembrolizumab (Pemb) and low-dose Cyclophosphamide (CPA) is expected to enhance immune response. This trial aims to assess the safety and efficacy of this regimen in patients (pts) with PROC. Methods: Phase 1 escalation cohort allowed all PROC subtypes and comprised 2 dose levels (DL) of MVP-S with 1 initial dose 0.25 mL followed by boosters of 0.25 mL (DL1) or 0.5mL (DL2) SC q6w, combined with CPA (50 mg BID every other week) and Pemb (200 mg q3w). Dose escalation was performed using 3+3 design. Dose-limiting toxicities (DLT) were defined as G4 non-hematologic, ≥G3 persistent non-hematologic toxicity, laboratory value or febrile neutropenia; ≥G2 persistent injection site skin ulceration ( > 1wk) or allergic/immune reactions by CTCAE v4.03. DL was considered safe if ≤1 DLT occurred in 6 pts until 21 days after initial and first boosting dose. Pts with high-grade serous (HGSOC) or endometrioid ovarian cancer were allowed in the Phase 2 expansion cohort (P2EC) and treated with the Recommended Phase 2 Dose (RP2D). Response was assessed every 6 wks. Activity in P2EC was defined as at least 2/10 partial response (PR) or stable disease (SD) for 12 wks according to RECIST 1.1. Primary endpoint is overall response rate (ORR), and secondary includes safety, PFS, and OS. Biopsies and blood draws were performed prior to and on treatment for genomic analysis, immune profiling and ctDNA. Results: Twenty-six pts were enrolled, 24 were evaluable for safety (8 DL1, 6 DL2, and 10 in P2EC). HGSOC represented 62% of phase I and 100% of P2EC. Median age was 61y (49-78). Pts received a median of 4 (1-7) prior lines of therapy. Median cycles of MVP-S were 2 (1-8). Toxicity G4/G3/G2 occurred in 1/3/7 pts of DL1 and 0/3/6 of DL2. G3/G2 immune-related AE (irAE) and injection site reactions (ISR) were observed in 1/1 and 1/3 pts treated at DL1, and in 1/0 and 2/2 pts at DL2, respectively. DL1 was selected as RP2D due to the occurrence of nephritis and ISR G3 at DL2. No AEs were qualified as DLT. On the P2EC, 5 G3 (1 irAE, 0 ISR) and 28 G2 (0 irAE, 3 ISR) toxicities were observed. At Phase 1, one pt with MSI-High clear cell subtype has ongoing CR after 26 mos of follow-up, 2 pts had PR and 6 SD.There were 1 PR and 3 SD on P2EC, of which 1 and 2, respectively, achieved response > 12wks. Conclusions: The combination of MVP-S, low-dose CPA, and Pemb was tolerable and met the efficacy endpoint in the expansion cohort in heavily treated PROC. Immuno-genomic correlative analyses are ongoing. Clinical trial information: NCT03029403. [Table: see text]
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 | 0,001 |
| 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 | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,003 | 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 ».