FAVEZELIMAB PLUS PEMBROLIZUMAB IN ANTI–PD‐1–REFRACTORY CLASSICAL HODGKIN LYMPHOMA (CHL): ESTIMATING THE RELATIVE EFFICACY OF FAVEZELIMAB
Notice bibliographique
Résumé
Introduction: There is an unmet need for effective therapeutic options for patients (pts) with relapsed or refractory (R/R) cHL whose disease has progressed after a PD-1 inhibitor. Favezelimab is a LAG-3 inhibitor that had tolerable safety and effective antitumor activity when used in combination with pembrolizumab in pts with anti–PD-1–refractory R/R cHL in the phase 1/2 MK-4280-003 study (Timmerman J et al. J Clin Oncol. 2022;40(16 suppl):7545). ORR in this study was promising, but the contribution of favezelimab is unclear. In this post hoc analysis, we assessed relative efficacy of favezelimab + pembrolizumab versus pembrolizumab alone in pts with anti–PD-1–refractory R/R cHL. Because there are no clinical trial data for pembrolizumab alone in this setting, we used historical data from pts with R/R cHL who received pembrolizumab beyond disease progression in the phase 2 KEYNOTE-087 study. Method: Pts from MK-4280-003 with a baseline and postbaseline scan were included. Pts from KEYNOTE-087 who received >2 doses of pembrolizumab beyond progression, had confirmed progression within 12 weeks of the last dose of pembrolizumab (confirmatory scan ≥4 weeks from initial progression), and had postprogression scans available, were included in the historical control arm. Pts in MK-4280-003 received pembrolizumab 200 mg IV Q3W plus favezelimab 200 mg or 800 mg IV Q3W. Pts in KEYNOTE-087 received pembrolizumab 200 mg IV Q3W. For pts in KEYNOTE-087, baseline tumor size was reset at first progression and best change in target lesion size was calculated in the postprogression period. ORR was assessed per Cheson 2007 criteria. A bootstrapping method compared change in target lesion size, with 1000 random samples averaged from pts in KEYNOTE-087. Results: 27 of 33 pts in MK-4280-003 were included for the radiographic analysis. In KEYNOTE-087, 123 pts developed disease progression on pembrolizumab, of whom 81 received postprogression pembrolizumab and were included in this analysis. ORR for pts who received favezelimab + pembrolizumab was 31% (range 15–51) compared with 2.5% (range 0–5.9) for pts who received potsprogression pembrolizumab. Average change from baseline in target lesion size was −46.6% for favezelimab + pembrolizumab compared with −0.37% for postprogression pembrolizumab. 44% of pts who received favezelimab + pembrolizumab had a ≥50% reduction in target lesion size compared with 5% of pts who received postprogression pembrolizumab. Results of the bootstrapping analysis showed a better response for favezelimab + pembrolizumab relative to pembrolizumab monotherapy in 99.4% (26,826 of 27,000) of samples. Keywords: Hodgkin lymphoma, immunotherapy Encore Abstract—previously submitted to EHA 2023 The research was funded by: Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA. Conflicts of interests pertinent to the abstract P. Armand Consultant or advisory role: BMS, MSD, ADC Therapeutics, GenMab, Enterome, Tessa Therapeutics, Regeneron, Genentech/Roche, AstraZeneca, Xencor, ATB Therapeutics, Foresight Diagnostics Honoraria: Merck Research funding: MSD, BMS, Roche, Adaptive Biotechnologies, Affimed Therapeutics, Genentech, IGM, Kite--a Gilead company P. L. Zinzani Consultant or advisory role: Celltrion, Gilead Sciences, Janssen-Cilag, BMS, SERVIER, Sandoz, MSD, Roche, EUSA Pharma, Kyowa Kirin, Takeda, Secure BIO, TG Therapeutics, Novartis, ADC Therapeutics, Incyte, BeiGene Other remuneration: Speaker bureau--MSD, EUSA Pharma, Novartis J. Timmerman Consultant or advisory role: Kite/Gilead, DAVA Oncology, Oncovalent Therapeutics Honoraria: Kite/Gilead Research funding: BMS, Kite- A Gilead company, Merck Travel grants: BMS N. Johnson Consultant or advisory role: Roche, Merck, AbbVie, Gilead Honoraria: Roche, Merck D. Lavie Consultant or advisory role: AbbVie, Novartis, Takeda K. Thiagarajan Employment or leadership position: Vantage Research Inc. Consultant or advisory role: Vantage Research Inc. B. Topp Employment or leadership position: Merck Stock ownership: Merck P. Pillai Employment or leadership position: Merck Stock ownership: Merck A. F. Herrera Consultant or advisory role: BMS, Seattle Genetics, Merck, Genentech/Roche, AstraZeneca/MedImmune, Karyopharm Therapeutics, ADC Therapeutics, Takeda, Regeneron, Genmab, Tubulis GmbH, Pfizer, Adicet Bio, Caribou Biosciences, AbbVie Research funding: BMS, Merck, Genentech/Roche, Kite--a Gilead Company, AstraZeneca, Seattle Genetics, Gilead Sciences, ADC Therapeutics Travel grants: BMS
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 distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,001 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,000 | 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) | 0,000 | 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 tête enseignante, 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 ».