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 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 | 0,009 | 0,008 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,002 | 0,002 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,001 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 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 ».