A phase II, open‐label, multicenter study of capivasertib, a potent, oral pan‐AKT inhibitor, in patients with relapsed or refractory B‐cell non‐Hodgkin lymphoma (CAPITAL)
Notice bibliographique
Résumé
Introduction: The PI3K/AKT/mTOR pathway is an established therapeutic target in indolent B-cell non-Hodgkin lymphoma (B-NHL). Several PI3K inhibitors (PI3Ki) have been approved to treat relapsed/refractory (R/R) follicular lymphoma (FL) and marginal zone lymphoma (MZL). Nonetheless, potential class-specific and PI3K isoform-related toxicities may limit their clinical utility. Capivasertib is an oral, potent, selective pan-AKT inhibitor that has demonstrated evidence of survival benefit in phase 2 clinical studies in patients with solid tumors. Capivasertib has also shown a manageable safety profile and unlike PI3Ki, colitis or pneumonitis do not feature as noted toxicities. Here, we report preliminary safety and efficacy data from a phase II study evaluating capivasertib in pts with R/R B-NHL (NCT05008055). Methods: Eligible pts were adults (≥18 years) with R/R NHL including histologically confirmed FL, MZL, and mantle cell lymphoma (MCL). Pts received capivasertib 480 mg orally twice daily using an intermittent schedule of 4 days on/3 days off in 28-day cycles until disease progression or unacceptable toxicity. Response was assessed by investigators based on the modified Lugano Classification lymphoma response criteria (Cheson, et al. JCO 2014). Baseline PTEN status and genomics will be correlated with clinical efficacy. Results: At data cut off (DCO; December 21, 2022), 15 pts with R/R B-NHL had been treated (histology: FL [n = 11], MZL [n = 2], MCL [n = 2]). Pts had a median age of 55 (range 40–87) years and had received a median of 3 prior lines of therapy (2–5), including prior PI3Ki (n = 6), and autologous stem cell transplant (n = 1). Six (40%) pts were refractory to their most recent therapy. Median follow-up for dosed pts was 5 (range 1–11) months. Treatment was ongoing in 9 (60%) pts. 11/13 pts with FL or MZL were evaluable for efficacy (FL 10/11, MZL 1/2). ORR was 54%; 8% of pts had a CR, 46% had a PR, 23% had SD, and 8% had PD. No response data are available for the MCL cohort because both pts were not evaluable at DCO. Grade ≥3 TEAEs occurred in 3 pts: COVID-19, QT prolongation, and rash; no grade ≥3 infections other than COVID-19 were reported. No immune-mediated adverse events or treatment-related deaths occurred. One (7%) pt discontinued due to TEAE (grade 3 QT prolongation). The most common TEAEs (≥25% of patients) were diarrhea (93%), fatigue (27%), and nausea (27%). Diarrhea events were all grade 1 (57%) or 2 (43%) and mainly occurred on dosing days. Conclusions: Capivasertib demonstrated single-agent activity and a manageable safety profile in pts with heavily pretreated R/R FL. Notably, no immune-mediated events and no treatment-related deaths were observed. Capivasertib has the potential to be an alternative therapeutic option for pts with R/R B-NHL, with a non-overlapping safety profile compared to currently available PI3Ki. Encore Abstract - previously submitted to EHA 2023 The research was funded by AstraZeneca Keywords: Indolent non-Hodgkin lymphoma, Molecular Targeted Therapies Conflicts of interests pertinent to the abstract. D. Hodson Research funding: AstraZeneca, paid to institution Other remuneration: Editorial support for abstract, paid to institution G. Shouse Consultant or advisory role: Abbvie Honoraria: Kite Pharma, Beigene A. Salar Honoraria: Beigene, Incyte, Janssen, Roche Other remuneration: Abbvie, Roche S. Bobillo Honoraria: Abbvie, AstraZeneca, Janssen, Roche R. Cordoba Honoraria: Abbvie, AstraZeneca, Beigene, BMS, Genmab, Incyte, Janssen, Kite, Kyowa-Kirin, Roche, Takeda J. Radford Consultant or advisory role: ADC Therapeutics, BMS, Kite Pharma, Takeda Stock ownership: ADC Therapeutics, AstraZeneca Honoraria: ADC Therapeutics, BMS Research funding: Takeda Other remuneration: ADC Therapeutics, Takeda S. Guidez Honoraria: AstraZeneca, Gilead Kite, Incyte, Takeda A. F. Herrera Consultant or advisory role: Adicet Bio; AstraZeneca, BMS, Caribou, Genentech, Genmab, Karyopharm, Merck, Regeneron, Seattle Genetics, Takeda, Tubulis Research funding: ADC Therapeutics, AstraZeneca, Genentech, Gilead, KiTE Pharma, Merck, Pfizer F. Morchhauser Consultant or advisory role: Abbvie, AstraZeneca, BMS, Genmab, Gilead, Novartis, Roche Honoraria: Chugai, Roche D. Johnson Employment or leadership position: AstraZeneca M. Izuzquiza Employment or leadership position: AstraZeneca N. Sambamurthy Employment or leadership position: AstraZeneca A. Forcina Employment or leadership position: AstraZeneca G. Gorgun Employment or leadership position: AstraZeneca R. Chen Employment or leadership position: AstraZeneca A. Younes Employment or leadership position: AstraZeneca M. Wang Consultant or advisory role: AstraZeneca, BMS, Gilead, Incyte, Nanostring, Novartis, Roche Honoraria: Abbvie Research funding: Astex, Argen X, GSK Educational grants: AstraZeneca
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) | 0,002 | 0,000 |
| Bibliométrie | 0,000 | 0,001 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,001 | 0,001 |
| Intégrité de la recherche | 0,001 | 0,000 |
| 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 ».