Abstract PR11: Allogeneic memory-like natural killer (NK) cell therapy with IL-15 superagonist with or without ipilimumab for advanced, incurable head and neck cancer: A phase 1 trial
Notice bibliographique
Résumé
Abstract Purpose: Patients with recurrent incurable, or metastatic (R/M) head and neck cancers (HNCs) refractory to platinum and immunotherapy have poor survival. Cellular therapies have emerged as treatments with potential activity in solid tumors. This proof-of-concept trial investigated an allogeneic cytokine-induced, memory-like (CIML) NK cell infusion followed by IL-15 superagonist (sa) after lead-in CTLA-4 inhibition (ipilimumab) plus lymphodepleting (LD) chemotherapy in advanced HNC. Methods: This phase 1 single-center trial enrolled patients (pts) with R/M HNC (n=7 HNSCC, n=3 salivary cancer) regardless of human papillomavirus (HPV) status who had prior platinum and immunotherapy. Pts in cohort 1 received LD fludarabine (25 mg/m2) and cyclophosphamide (60 mg/m2/kg) on days -6 to -2 prior to haploidentical CIML NK cell infusion on day 0 (5-10 × 106 viable cells/kg=dose level 0) followed by N-803 (IL-15sa, 15 mcg/kg subcutaneously) starting on day +1 every 21-days for 4-doses; in cohort 2, pts received the same regimen with a dose of lead-in ipilimumab on day -7. Cohort 1 treated 3 pts at dose level 0; <2 DLTs triggered an additional 3 pts (n=6). Cohort 2 treated an additional 4 pts. Primary objective: safety, maximum tolerated dose of CIML NK cells. Secondary objectives: objective response rate, progression-free survival (PFS), overall survival (OS), and phenotypic expansion and function of adoptively transferred NK cells. Results: From 9/8/20 to 12/2/22, 10 pts enrolled. One DLT was observed at dose level 0. Median age: 58; 9/10 (90%) were men; 8 (80%) had oropharyngeal primaries (6 HPV+) with a median 6 prior lines of therapy for R/M disease (range: 3-8). Eight (80%) had offspring donors. Grade (G) 3-4 hematologic adverse events were common (10/10, 100%). One patient died of G5 febrile neutropenia and infection (DLT). Median days hospitalized: 15 (range: 9-37). Mild CRS was observed in 6/10 (60%); 5/6 received anti-IL6 therapy; no neurotoxicity was observed. One (10%) partial response (PR) lasted 6.5 months; 6 (60%) had stable disease, 3 (30%) had progression. Tumor regression was observed in 5/10 (50%) at day +30. At a median follow-up of 20.2 mos, median PFS: 2.6 mos (95%CI 1-3.9); median OS: 3.5 mos (95%CI 1-4.7). CIML NK expansion in the peripheral blood (PB) occurred on day +7 in 9/10 of pts. A donor-specific antibody was found in the one patient without expansion. In pts with tumor regression at day +30 compared to those without, CD56dimCD16+ NK cell clusters expanded by day +14 (93.7% vs. 37.3% of PB NK cells). The CD16+KIR+CD57+ NK cell cluster was more prevalent in the ipilimumab-treated pts at the time of tumor regression (16% vs. 4%, p<0.05). Conclusion: Allogeneic CIML NK cells can induce tumor regression associated with persistent CIML NK cell expansion in advanced HNC pts. Tumor regression was associated with CD56dimCD16+ NK cell expansion. We demonstrate safety and feasibility with the expected toxicity of LD. These findings have important implications for the development of cellular therapies in solid tumors. Citation Format: Glenn J. Hanna, Roman M. Shapiro, Michal Sheffer, Michela Ansuinelli, Grace Birch, Robert A. Redd, Alejandro Alonso, Denbaa Bat-Erdene, Samantha Himberg, Heather Daley, Diego E. Hernandez-Rodriquez, Katharin L. Shaw, Jerome Ritz, Sarah Nikiforow, Robert J. Soiffer, Rizwan Romee. Allogeneic memory-like natural killer (NK) cell therapy with IL-15 superagonist with or without ipilimumab for advanced, incurable head and neck cancer: A phase 1 trial [abstract]. In: Proceedings of the AACR-AHNS Head and Neck Cancer Conference: Innovating through Basic, Clinical, and Translational Research; 2023 Jul 7-8; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2023;29(18_Suppl):Abstract nr PR11.
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 | 0,000 |
| 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 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,003 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,004 | 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 ».