| Title: |
Efficacy and Safety of Capivasertib (AZD5363), a Potent, Oral Pan-AKT Inhibitor, in Patients with Relapsed or Refractory B-cell Non-Hodgkin Lymphoma (CAPITAL). |
| Authors: |
Hodson, Daniel J; Shouse, Geoffrey; Shin, Ho-Jin; Salar, Antonio; Bobillo, Sabela; Ribrag, Vincent; Macpherson, Nicol A; Cordoba, Raul; Kim, Jin Seok; Guidez, Stephanie; Herrera, Alex F; Morschhauser, Franck; Colton, Dachelle; Izuzquiza, Macarena; Sambamurthy, Nisha; Munugalavadla, Veerendra; Vicente, Sergio; Gorgun, Gullu; Chen, Robert; Younes, Anas; Wang, Michael L |
| Publisher Information: |
American Association for Cancer Research (AACR); Department of Haematology; //doi.org/10.1158/1078-0432.ccr-25-2239 |
| Publication Year: |
2026 |
| Collection: |
Apollo - University of Cambridge Repository |
| Subject Terms: |
Humans; Male; Female; Middle Aged; Aged; Proto-Oncogene Proteins c-akt; Adult; Pyrimidines; Protein Kinase Inhibitors; Neoplasm Recurrence; Local; 80 and over; Lymphoma; B-Cell; Treatment Outcome; Administration; Oral; Drug Resistance; Neoplasm; Pyrroles |
| Description: |
PURPOSE: An unmet treatment need remains for relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL), including the follicular lymphoma (FL), mantle cell lymphoma (MCL), and marginal zone lymphoma (MZL) subtypes. The PI3K/AKT/mTOR pathway is dysregulated and associated with poor prognosis in NHL. The AKT inhibitor capivasertib has preclinical activity in hematologic malignancy models. PATIENTS AND METHODS: NCT05008055 was a modular, open-label, multicenter phase II study that examined oral capivasertib monotherapy in patients with R/R B-cell NHL who had received ≥2 prior lines of therapy. Patients had R/R FL (cohort 1A), MZL (cohort 1B), or MCL (cohort 1C). Capivasertib 480 mg twice daily was administered orally 4 days on/3 days off. The primary objective was to determine the objective response rate (ORR) by blinded independent central review. RESULTS: Thirty patients were enrolled (of 272 planned). The ORR for patients with R/R FL, MZL, and MCL were 18.8% (three of 16), 33.3% (one of three), and 30% (three of 10), respectively; 62.5% (10 of 16) of patients with R/R FL had stable disease. Baseline tumor PTEN expression was deficient/undetectable in the two patients who had a complete response and three of five patients who had a partial response. The most common capivasertib-related adverse events (AE) were diarrhea (63.3%), nausea (20%), vomiting (13.3%), and hyperglycemia (10%). Capivasertib-related grade ≥3 AE or serious AE were observed in nine and three patients, respectively. CONCLUSIONS: The study was terminated early with a small sample size, limiting interpretation, although antitumor activity was limited. Future studies of capivasertib in hematologic malignancies would likely require biomarker-directed patient selection and/or combination therapy. |
| Document Type: |
article in journal/newspaper |
| File Description: |
Print-Electronic; application/pdf |
| Language: |
English |
| Relation: |
https://www.repository.cam.ac.uk/handle/1810/396750 |
| Availability: |
https://www.repository.cam.ac.uk/handle/1810/396750 |
| Rights: |
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) ; https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.8B7A6604 |
| Database: |
BASE |