Abstract A074: Maveropepimut-S, a DPX-based immune-educating therapy, combined with Pembrolizumab and Cyclophosphamide in recurrent ovarian cancer, results from the Phase 1/2 PESCO Trial
Notice bibliographique
Résumé
Abstract Background: Maveropepimut-S (MVP-S) is a DPX-based immunotherapy that targets survivin-expressing tumor cells and induces a cytotoxic T cell response. Combination with Pembrolizumab (Pemb) and low-dose Cyclophosphamide (CPA) is expected to enhance immune response. This trial aims to evaluate the safety and efficacy of MVP-S, Pemb, and low-dose CPA in patients (pts) with recurrent epithelial ovarian cancer (EOC). Methods: Non-randomized, open-label, phase 1/2 study. Phase 1 escalation cohort used a 3+3 design and included platinum-resistant EOC treated at 2 MVP-S dose levels (DL). All doses were delivered subcutaneously. MVP-S DL1, elected as recommended phase 2 dose (RP2D), included a priming dose of 0.25mL followed by boosters of 0.25mL q6w. MVP-S was combined with CPA (50 mg BID every other week) and Pemb (200 mg q3w). Phase 2 comprised three expansion cohorts. Cohorts A and B allowed high-grade serous (HGSC) or endometrioid tumors sensitive and resistant to platinum, respectively. Exploratory Cohort C enrolled pts with rare EOC subtypes. The primary endpoint was overall response rate (ORR), with secondary endpoints of safety, PFS, and OS. Tumor response was assessed every 6 wks according to RECIST1.1. Activity signal in Cohort A was defined as at least 3/10 partial response (PR) or sustained (>12 wks) stable disease (SD), and for Cohort B as at least 2/10 PR or sustained SD. Biopsies and blood draws were performed before and on treatment for correlative analysis, including flow cytometry, genotyping and ctDNA. The survivin-specific immune response was detected by IFN-γ production after stimulation of PBMCs with survivin peptides. Results:16 pts in the phase 1 escalation cohort (10 DL1 and 6 DL2) and 31 in the phase 2 expansion cohorts (A:11, B:10, C:10) were enrolled. The median age was 60y (range 39-78), and the median prior therapy lines received was 3 (range 1-6). The median follow-up was 14.0 months. Most frequent histologies were HGSC (68%) and clear cell carcinoma (23%). 45 pts were evaluated for safety. The most common AE was injection site reaction, observed in 33 pts (14 G1; 12 G2; 7 G3). Other AEs included fatigue (n=20), anemia (n=18), and nausea (n=16). G1 and G2 accounted for 90% of all related AEs. G3/G4 immune-related AEs occurred in 3 and 1 pts, respectively. Among 44 pts evaluable for efficacy, 1 complete response,9 PR, and 16 SD were observed (ORR 23%). In cohort A, 4/10 pts had PR, and 5/10 had SD (4 of 5 for >12 wks). In cohort B, there was 1/10 PR and 3/10 sustained SD. Cohort C was composed predominantly of clear cell carcinoma, and 2/10 pts had PR, and 2/10 had SD as the best responses. Survivin peptide re-stimulation assays were conducted in 24 pts; survivin-specific immune responses were detected in 14 pts (58%) and correlated with clinical responses (PR/SD) in 13. Conclusion: Combination of MVP-S, low-dose CPA, and Pemb in EOC is well-tolerated and shows promising clinical activity. Primary efficacy endpoints were met in cohorts A and B. Survivin-specific immune responses were correlated with clinical outcomes. Citation Format: Ana C. Veneziani, Husam Alqaisi, Douglas G Millar, Ilaria Colombo, Eduardo Gonzalez-Ochoa, Swati Atale, Anthony Msan, Judy Quintos, Janelle Ramsahai, Vikas Garg, Pamela Soberanis, Neesha C Dhani, Robert C Grant, Lisa Wang, Valerie Bowering, Stephanie Lheureux, Pamela S Ohashi, Amit M Oza. Maveropepimut-S, a DPX-based immune-educating therapy, combined with Pembrolizumab and Cyclophosphamide in recurrent ovarian cancer, results from the Phase 1/2 PESCO Trial [abstract]. In: Proceedings of the AACR Special Conference on Ovarian Cancer; 2023 Oct 5-7; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_2):Abstract nr A074.
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 | 0,001 | 0,001 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,006 | 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 ».