Phase 2 study of parsaclisib (INCB050465), a highly selective, next-generation PI3Kδ inhibitor, in relapsed or refractory diffuse large B-cell lymphoma (CITADEL-202)

Coleman, Morton; Belada, David; Casasnovas, Olivier; Gressin, Rémy; Lee, Hui-Peng; Mehta, Amitkumar; Muñoz, Javier; Verhoef, Gregor; Corrado, Claudia; DeMarini, Douglas J.; Zhao, Wanying; Li, Jia; Fay, Keith

doi:10.1080/10428194.2020.1832660

Cited by 24 publications

(25 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The CITADEL-205 study in R/R MCL showed activity of parsaclisib only in patients who had not received previous BTKi, with an objective response rate (ORR) and CR of 70% and 15.6%, respectively [ 150 ], but the results in the most realistic cohort, the BTKi-experienced patients, were disappointing, with ORR and CR of only 35.5% and 2.9%, respectively [ 151 ]. In R/R DLBCL, despite an initial ORR of 30% in the phase 1/2 study [ 149 ], the CITADEL-202 study was prematurely closed due to the high proportion of patients with disease progression during treatment: 95% (52 out of 55 patients) in the BTKi-naïve arm and 80% (4 out of 5 patients) in the BTKi-experienced arm [ 144 ]. These and other PI3Ki are currently undergoing evaluation in combination with chemotherapy and other targeted drugs ( Table 2 ).…”

Section: Pharmacological Targeting Of Bcr Upstream Kinases and Its Li...mentioning

confidence: 99%

Regulation of B-Cell Receptor Signaling and Its Therapeutic Relevance in Aggressive B-Cell Lymphomas

Profitós-Pelejà

Santos

Marín‐Niebla

et al. 2022

Cancers

View full text Add to dashboard Cite

The proliferation and survival signals emanating from the B-cell receptor (BCR) constitute a crucial aspect of mature lymphocyte’s life. Dysregulated BCR signaling is considered a potent contributor to tumor survival in different subtypes of B-cell non-Hodgkin lymphomas (B-NHLs). In the last decade, the emergence of BCR-associated kinases as rational therapeutic targets has led to the development and approval of several small molecule inhibitors targeting either Bruton’s tyrosine kinase (BTK), spleen tyrosine kinase (SYK), or phosphatidylinositol 3 kinase (PI3K), offering alternative treatment options to standard chemoimmunotherapy, and making some of these drugs valuable assets in the anti-lymphoma armamentarium. Despite their initial effectiveness, these precision medicine strategies are limited by primary resistance in aggressive B-cell lymphoma such as diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), especially in the case of first generation BTK inhibitors. In these patients, BCR-targeting drugs often fail to produce durable responses, and nearly all cases eventually progress with a dismal outcome, due to secondary resistance. This review will discuss our current understanding of the role of antigen-dependent and antigen-independent BCR signaling in DLBCL and MCL and will cover both approved inhibitors and investigational molecules being evaluated in early preclinical studies. We will discuss how the mechanisms of action of these molecules, and their off/on-target effects can influence their effectiveness and lead to toxicity, and how our actual knowledge supports the development of more specific inhibitors and new, rationally based, combination therapies, for the management of MCL and DLBCL patients.

show abstract

Section: Pharmacological Targeting Of Bcr Upstream Kinases and Its Li...mentioning

confidence: 99%

Regulation of B-Cell Receptor Signaling and Its Therapeutic Relevance in Aggressive B-Cell Lymphomas

Profitós-Pelejà

Santos

Marín‐Niebla

et al. 2022

Cancers

View full text Add to dashboard Cite

show abstract

“…Parsaclisib (INCB050465) is a highly selective PI3Kδ inhibitor that demonstrated antitumor activity to improve long-term survival in R/R B-cell NHL patients in a phase I/II study. 45 Another multicenter phase II study evaluating parsaclisib monotherapy in R/R DLBCL patients demonstrated an ORR of 25%, 46 providing a potential new strategy for the treatment of R/R DLBCL patients.…”

Section: Signaling Pathway Inhibitorsmentioning

confidence: 99%

Immune targeted therapy for diffuse large B cell lymphoma

Zheng

Tian

et al. 2021

Blood Science

View full text Add to dashboard Cite

Diffuse large B-cell lymphoma (DLBCL), the most common subtype of non-Hodgkin lymphoma, is highly heterogeneous and invasive. Although the majority of DLBCL patients show a good response to rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone treatment, approximately one-third of patients still have a poor prognosis. Many immune-targeted drugs, such as bispecific T-cell engagers and CAR T-cell therapy, have been proven effective for refractory and relapsed patients. This article reviews the progress of immune targeted therapy for DLBCL.

show abstract

“…The CITADEL-205 study in R/R MCL showed activity of parsaclisib only in patients who had not received previous BTKi, with objective response rate (ORR) and CR of 70% and 15.6% respectively [132], but the results in the most realistic cohort, the BTKiexperienced patients, were disappointing, with ORR and CR of only 35.5% and 2.9% respectively [133]. In R/R DLBCL, despite an initial ORR of 30% in the phase 1/2 study [131], the CITADEL-202 study was prematurely closed due to the high proportion of patients with disease progression during treatment: 95% (52 out of 55 patients) in the BTKi-naïve arm and 80% (4 out of 5 patients) in the BTKi-experienced arm [134]. These and other PI3Ki are currently undergoing evaluation in combination with chemotherapy and other targeted drugs (Table 1).…”

Section: Clinical Experience With the Targeting Of Apical Bcr Kinases In Dlbcl And MCLmentioning

confidence: 99%

Regulation of B Cell Receptor Signaling and Its Therapeutic Relevance in Aggressive B-Cell Lymphomas

Profitós-Pelejà¹,

Santos²,

Marín‐Niebla³

et al. 2021

Preprint

View full text Add to dashboard Cite

The proliferation and survival signals emanating from the B-cell receptor (BCR) constitute a crucial aspect of mature lymphocyte’s life. Dysregulated BCR signaling is considered a potent contributor to tumor survival in different subtypes of B cell non-Hodgkin lymphomas (B-NHLs). In the last decade, emergence of BCR-associated kinases as rational therapeutic targets has led to the development and approval of several small molecule inhibitors targeting either Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), or phosphatidylinositol 3 kinase (PI3K), offering alternative treatment options to standard chemoimmunotherapy, and making some of these drugs valuable assets in the anti-lymphoma armamentarium. Despite their initial effectiveness, these precision medicine strategies are limited by primary resistance in aggressive B-cell lymphoma like diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), especially in the case of first generation BTK inhibitors. In these patients, BCR-targeting drugs often fail to produce durable responses, and nearly all cases eventually progress with a dismal outcome, due to secondary resistance. This review will discuss our current understanding of the role of antigen-dependent and antigen-independent BCR signaling in DLBCL and MCL and will cover both approved inhibitors and investigational molecules being evaluated in early preclinical studies. We will discuss how the mechanisms of action of these molecules, and their off/on-target effects can influence their effectiveness and lead to toxicity, and how our actual knowledge supports the development of more specific inhibitors and new, rationally based, combination therapies, for the management of MCL and DLBCL patients.

show abstract

Phase 2 study of parsaclisib (INCB050465), a highly selective, next-generation PI3Kδ inhibitor, in relapsed or refractory diffuse large B-cell lymphoma (CITADEL-202)

Cited by 24 publications

References 20 publications

Regulation of B-Cell Receptor Signaling and Its Therapeutic Relevance in Aggressive B-Cell Lymphomas

Regulation of B-Cell Receptor Signaling and Its Therapeutic Relevance in Aggressive B-Cell Lymphomas

Immune targeted therapy for diffuse large B cell lymphoma

Regulation of B Cell Receptor Signaling and Its Therapeutic Relevance in Aggressive B-Cell Lymphomas

Contact Info

Product

Resources

About